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Moving Rats (moving + rat)
Kinds of Moving Rats Selected AbstractsCardiac Dysrhythmia Associated with the Immediate Postictal State after Maximal Electroshock in Freely Moving RatEPILEPSIA, Issue 4 2002Olivier Darbin Summary: ,Purpose: Cardiac autonomic changes accompany complex partial seizures and generalized tonic,clonic seizures, and participate, at least partially, in the sudden and unexpected death in epilepsy (SUDEP). The analysis of the heart rate variability (HRV) is one of the simplest ways of providing insight into autonomic functions. The entropy quantifies the repetition of complex patterns in a signal and refers to systems randomness, regularity, and predictability. Clinical investigations have reported that entropy decreases in patients with a high risk of sudden cardiac death. The goal of this study was to evaluate the effects of the maximal electroshock (MES) on the entropy of HRV, monitored in the immediate postictal stage in the model of the freely moving rat. Methods: Entropy changes were correlated with the high and low frequencies of spectral analysis, which reflect the participation of the sympathetic and parasympathetic activities. Results: MES-induced arrhythmia is characterized by an HRV increase, an imbalance in favor of the parasympathetic activity, and a decrease in the entropy. Entropy decrease was restricted to the duration of the arrhythmia, suggesting that the postictal arrhythmia may be associated with a higher risk of lethal cardiac complications. Nevertheless, entropy changes did not correlate with spectral changes. Conclusions: The results suggest that the imbalance demonstrated in the spectral domain explains only partially the contribution of each autonomic system in the complexity of the heart rate during the postictal state. [source] Furosemide Terminates Limbic Status Epilepticus in Freely Moving RatsEPILEPSIA, Issue 9 2003Martin Holtkamp Summary:,Purpose: To evaluate the anticonvulsant properties of furosemide and to determine sedative side effects compared with pentobarbital and diuretic side effects compared with saline-treated controls in an experimental model of limbic status epilepticus. Methods: Self-sustaining status epilepticus was induced in rats by continuous electrical stimulation of the perforant path. Five minutes after the end of the stimulation, animals were given 100 mg/kg furosemide, 30 mg/kg pentobarbital, or an equal amount of saline, intraperitoneally. After administration of the substance, animals were monitored clinically and electrographically for 3 h regarding status epilepticus, level of sedation, and diuresis. Results: In seven of 10 animals, furosemide terminated status epilepticus after 68 ± 26 min, whereas pentobarbital was successful in all animals after 5 ± 0.8 min. In contrast to pentobarbital, sedation did not occur with furosemide. Weight loss after furosemide was 10.2 ± 1.7% compared with 6.5 ± 1.1% in animals given saline (p < 0.001). Conclusions: The results suggest that furosemide may serve as an alternative or additional agent for refractory complex partial status epilepticus in patients in whom common anesthetics are not justifiable. [source] Possible Contribution of Central Gamma-Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving RatsEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Yumi Takemoto Previous studies have shown that central administration of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co-varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone. [source] Comparison of the Effects of Deramciclane, Ritanserin and Buspirone on Extracellular Dopamine and Its Metabolites in Striatum and Nucleus Accumbens of Freely Moving RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2008Tiina M. Kääriäinen Dual probe in vivo microdialysis in freely moving rats was used to compare the effects of graded doses of deramciclane fumarate (3, 10 and 30 mg/kg), 5-HT2A/C antagonist ritanserin (1 mg/kg) and a partial 5-HT1A agonist buspirone hydrochloride (5 mg/kg) on the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus accumbens and striatum assayed by high performance liquid chromatography with electrochemical detection. The indirect dopamine agonist, D-amphetamine sulfate (2 mg/kg), was used as a positive control. Ritanserin, buspirone and deramciclane 3 and 10 mg/kg had no significant effects on the extracellular dopamine levels in either brain area but deramciclane 30 mg/kg significantly increased accumbal dopamine as well as DOPAC and HVA in both brain areas. As expected, the positive control D-amphetamine significantly increased both striatal and accumbal dopamine levels. The effects of buspirone or the highest deramciclane dose and D-amphetamine on DOPAC and HVA levels were opposite; buspirone and deramciclane increased while D-amphetamine decreased the metabolite levels in both brain areas. The results indicate that a single high dose of deramciclane has the neuroleptic- or buspirone-like effect, particularly in mesolimbic regions. There is at least a 5-fold margin between the anxiolytic and neuroleptic doses of deramciclane in the rat. [source] On-line biosensors for simultaneous determination of glucose, choline, and glutamate integrated with a microseparation systemELECTROPHORESIS, Issue 18 2003Guoyue Shi Abstract An effective microseparation system integrated with ring-disc electrodes and two microfluidic devices was fabricated for in vivo determination using a microdialysis pump. The major interference of ascorbic acid (AA) was excluded by direct oxidation with ascorbate oxidase. Glucose, glutamate, and choline were successfully determined simultaneously through the biosensors modified with a bilayer of osmium-poly(4-vinylpyridine)gel-horseradish peroxidase (Os-gel-HRP)/glucose oxidase (GOD), glutamate oxidase (GlutaOD) or choline oxidase (ChOD). To stabilize the biosensors, 0.2% polyethylenimine (PEI) was mixed with the oxidases. The cathodic currents of glucose, glutamate, and choline biosensors started to increase after the standard solutions were injected into the microseparation system. The on-line biosensors show a wide calibration range (10,7,10,5 mol/L) with a detection limit of 10,8 mol/L at the working potential of ,50 mV. The variations of glucose, glutamate, and choline were determined simultaneously in a free moving rat when we perfused the medial frontal cortex with 100 ,mol/L N -methyl- D -aspartate (NMDA) solution, which is the agonist of the NMDA receptor. [source] Cardiac Dysrhythmia Associated with the Immediate Postictal State after Maximal Electroshock in Freely Moving RatEPILEPSIA, Issue 4 2002Olivier Darbin Summary: ,Purpose: Cardiac autonomic changes accompany complex partial seizures and generalized tonic,clonic seizures, and participate, at least partially, in the sudden and unexpected death in epilepsy (SUDEP). The analysis of the heart rate variability (HRV) is one of the simplest ways of providing insight into autonomic functions. The entropy quantifies the repetition of complex patterns in a signal and refers to systems randomness, regularity, and predictability. Clinical investigations have reported that entropy decreases in patients with a high risk of sudden cardiac death. The goal of this study was to evaluate the effects of the maximal electroshock (MES) on the entropy of HRV, monitored in the immediate postictal stage in the model of the freely moving rat. Methods: Entropy changes were correlated with the high and low frequencies of spectral analysis, which reflect the participation of the sympathetic and parasympathetic activities. Results: MES-induced arrhythmia is characterized by an HRV increase, an imbalance in favor of the parasympathetic activity, and a decrease in the entropy. Entropy decrease was restricted to the duration of the arrhythmia, suggesting that the postictal arrhythmia may be associated with a higher risk of lethal cardiac complications. Nevertheless, entropy changes did not correlate with spectral changes. Conclusions: The results suggest that the imbalance demonstrated in the spectral domain explains only partially the contribution of each autonomic system in the complexity of the heart rate during the postictal state. [source] Endogenous histamine in the medial septum,diagonal band complex increases the release of acetylcholine from the hippocampus: a dual-probe microdialysis study in the freely moving ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002Lucia Bacciottini Abstract The effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c-fos in the medial septum,diagonal band (MSA-DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA-DB neurons, we used the dual-probe microdialysis technique to apply drugs to the MSA-DB and record the induced effects in the projection area. Perfusion of MSA-DB with high-KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra-MSA-DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA-DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA-DB, increased the release of hippocampal ACh, whereas R-,-methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA-DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c-fos immunoreactivity were significantly more numerous in ciproxifan- or thioperamide-treated rats than in controls, although no colocalization of anti-c-fos and anti-ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus. [source] Possible Contribution of Central Gamma-Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving RatsEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Yumi Takemoto Previous studies have shown that central administration of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co-varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone. [source] Medial septal modulation of the ascending brainstem hippocampal synchronizing pathways in the freely moving ratHIPPOCAMPUS, Issue 1 2006Brian H. Bland Abstract Rats implanted with hippocampal recording electrodes were tested in a wheel-running apparatus under three conditions: (1) independent electrical stimulation of the medial septal nucleus (MS); (2) independent electrical stimulation of the posterior hypothalamic nucleus (PH); and (3) combined electrical stimulation of the MS and PH using pairings of two stimulation conditions, 7 or10 Hz stimulation of the MS, and a low- or high-intensity PH stimulation. Quantitative measures of running speed were taken, and hippocampal recordings were subjected to fast-Fourier transform analysis. Electrical stimulation of the PH induced wheel-running behavior; running speed and the accompanying hippocampus (HPC) theta frequency increased with increase in stimulation intensity. Electrical stimulation of the MS failed to induce wheel-running behavior despite the fact that HPC theta was induced at the frequency of the applied stimulation (7 and 10 Hz). Electrical stimulation of the MS reset the frequency of HPC theta induced by PH stimulation in both the upward and downward directions and increased theta power, while wheel-running speed was modulated in a downward direction only. © 2005 Wiley-Liss, Inc. [source] Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the ratJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2001Franēois-xavier Mathy Abstract The objective of this study was to validate subcutaneous (sc) microdialysis sampling to study flurbiprofen pharmacokinetics and plasma protein binding in the awake freely moving rat. A linear microdialysis probe was manufactured using a Hemophane® hollow fiber which was tested in vitro and in vivo for the recovery of flurbiprofen and naproxen used as retrodialysis marker. Flurbiprofen was administered intraperitoneally and intravenously at a dose of 20 mg/kg in rats. In both cases, conventional blood sampling and sc microdialysis sampling were simultaneously performed. The microdialysates were analyzed on-line by high-pressure liquid chromatography. Naproxen, which was shown to have a similar in vivo loss by retrodialysis as flurbiprofen (71.5,±,0.9% and 71.0,±,0.8% respectively, n,=,3), was used to continuously monitor probe recovery. Concentration-dependent protein binding of flurbiprofen was demonstrated in vivo based on experiments with a simultaneous sc microdialysis and blood sampling. Values of unbound fraction were similar to those reported previously by intravenous microdialysis sampling, demonstrating that the sc unbound concentrations are very similar to those in the central compartment. There was no significant difference among pharmacokinetic parameters (AUC, CL, t1/2z, Vd) for total or unbound flurbiprofen determined after intraperitoneal and intravenous administration. Subcutaneous microdialysis is a simple yet powerful tool to study the pharmacokinetics and the in vivo plasma protein binding of flurbiprofen in the awake unrestrained rat. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1897,1906, 2001 [source] Endogenous melatonin protects L -DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L -DOPA therapy in Parkinson's diseaseJOURNAL OF PINEAL RESEARCH, Issue 3 2006Gaia Rocchitta Abstract:, We previously showed, using microdialysis, that autoxidation of exogenous L-dihydroxyphenylalanine (l -DOPA) occurs in vivo in the extracellular compartment of the freely moving rat, with a consequent formation of l -DOPA semiquinone (l -DOPA-SQ). In the present study, intrastriatal infusion of l -DOPA (1.0 ,m for 200 min) increased dialysate l -DOPA concentrations (maximum increases up to 116-fold baseline values); moreover, l -DOPA-SQ was detected in dialysates. Individual dialysate concentrations of l -DOPA were negatively correlated with those of l -DOPA-SQ. Co-infusion of N -acetylcysteine (100 ,m) or melatonin (50 ,m) increased l -DOPA (up to 151- and 246-fold, respectively) and decreased l -DOPA-SQ (by about 53% and 87%, respectively) dialysate concentrations. Systemic l -DOPA [25 mg/kg intraperitoneally (i.p.) twice in a 12-h interval] significantly increased striatal baseline dialysate concentrations of l -DOPA and decreased dopamine (DA) and ascorbic acid (AsAc) concentrations, when compared with controls. Following systemic l -DOPA, l -DOPA-SQ was detected in dialysates. Endogenous melatonin was depleted in rats maintained on a 24-h light cycle for 1 wk. In melatonin-depleted rats, systemic l -DOPA induced a smaller increase in dialysate l -DOPA, a greater increase in l -DOPA-SQ formation, and a greater reduction in DA and AsAc dialysate concentrations. Co-administration of melatonin (5.0 mg/kg, i.p., twice in a 12-h interval) with l -DOPA, in control as well as in light-exposed rats, significantly increased dialysate l -DOPA concentrations, greatly inhibited l -DOPA-SQ formation, and restored up to the control values dialysate DA and AsAc concentrations. These findings demonstrate that endogenous melatonin protects exogenous l -DOPA from autoxidation in the extracellular compartment of the striatum of freely moving rats; moreover, systemic co-administration of melatonin with l -DOPA markedly increases striatal l -DOPA bioavailability in control as well as in melatonin-depleted rats. These results may be of relevance to the long-term l -DOPA therapy of Parkinson's disease. [source] Effects of chronic fluoxetine treatment in the presence and absence of (±)pindolol: a microdialysis studyBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000L A Dawson Using in vivo microdialysis in the frontal cortex of the freely moving rat we evaluated the effects of chronic treatment with the serotonin specific reuptake inhibitor (SSRI) fluoxetine in the presence and absence of the 5-HT1A/,-adrenergic antagonist (±)pindolol. Chronic vehicle treated animals produced no significant response to a challenge with fluoxetine (10 mg kg,1) on day 8 and 15. Alternatively, a significant (P<0.05) decrease in extracellular 5-HT was observed in control animals upon challenge with the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.03 and 0.1 mg kg,1). Conversely, animals treated with fluoxetine (10 mg kg,1 o.d.) for 7 and 14 days produced a significant (P<0.05) 2 fold increase in extracellular 5-HT when challenged with fluoxetine (10 mg kg,1) on day 8 and 15. Moreover, no significant decrease in extracellular 5-HT was observed upon challenge with either dose of 8-OH-DPAT. Animals chronically treated with (±)pindolol (10 or 20 mg kg,1 b.i.d.) produced a significant dose-related increase in extracellular 5-HT upon challenge with fluoxetine on day 15 only. Furthermore, both doses produced a significantly blunted response to the low dose challenge of 8-OH-DPAT (0.03 mg kg,1). In addition, 20 mg kg,1 (±)pindolol treated animals also had no response to the higher 0.1 mg kg,1 dose of 8-OH-DPAT. Animals treated for 14 days with a combination of (±)pindolol (10 or 20 mg kg,1) and fluoxetine were not significantly different from vehicle treated animals when challenged with fluoxetine or 8-OH-DPAT. Taken together it would therefore appear that although (±)pindolol alone has sufficient intrinsic activity to produce a desensitization of the 5-HT1A receptor, when given in combination with fluoxetine it is able to prevent the desensitization induced by not only fluoxetine but also itself. This may suggest that the clinical augmentation of antidepressant action by pindolol, when co-administered with a SSRI, is via antagonism of the 5-HT1A receptor. British Journal of Pharmacology (2000) 130, 797,804; doi:10.1038/sj.bjp.0703378 [source] Manganese increases L-DOPA auto-oxidation in the striatum of the freely moving rat: potential implications to L-DOPA long-term therapy of Parkinson's diseaseBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000Pier Andrea Serra We have previously shown that manganese enhances L-dihydroxyphenylanine (L-DOPA) toxicity to PC12 cells in vitro. The supposed mechanism of manganese enhancing effect [an increase in L-DOPA and dopamine (DA) auto-oxidation] was studied using microdialysis in the striatum of freely moving rats. Systemic L-DOPA [25 mg kg,1 intraperitoneally (i.p.) twice in a 12 h interval] significantly increased baseline dialysate concentrations of L-DOPA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and uric acid, compared to controls. Conversely, DA and ascorbic acid concentrations were significantly decreased. A L-DOPA oxidation product, presumptively identified as L-DOPA semiquinone, was detected in the dialysate. The L-DOPA semiquinone was detected also following intrastriatal infusion of L-DOPA. In rats given L-DOPA i.p., intrastriatal infusion of N-acetylcysteine (NAC) significantly increased DA and L-DOPA dialysate concentrations and lowered those of L-DOPA semiquinone; in addition, NAC decreased DOPAC+HVA and uric acid dialysate concentrations. In rats given L-DOPA either systemically or intrastriatally, intrastriatal infusion of manganese decreased L-DOPA dialysate concentrations and greatly increased those of L-DOPA semiquinone. These changes were inhibited by NAC infusion. These findings demonstrate that auto-oxidation of exogenous L-DOPA occurs in vivo in the rat striatum. The consequent reactive oxygen species generation may account for the decrease in dialysate DA and ascorbic acid concentrations and increase in enzymatic oxidation of xanthine and DA. L-DOPA auto-oxidation is inhibited by NAC and enhanced by manganese. These results may be of relevance to the L-DOPA long-term therapy of Parkinson's disease. British Journal of Pharmacology (2000) 130, 937,945; doi:10.1038/sj.bjp.0703379 [source] Effects of normobaric hyperoxia on water content in different organs in ratsACTA PHYSIOLOGICA, Issue 1 2002L. E. B. Stuhr ABSTRACT Pulmonary oxygen toxicity is a dose-dependent effect on alveolar epithelial and endothelial cells resulting in pulmonary oedema. Any concomitant effects on systemic capillary endothelium would be expected to result in capillary leakage and an increase in the tissues' water content. Total tissue water (TTW) in different organs was therefore studied in freely moving rats exposed to 100% O2 at normobaric pressure for 24 or 48 h, and compared to air-breathing control rats. The TTW for the following tissues was measured: Trachea, left bronchus, left lung, left and right ventricle, left kidney, skin (left paw-hindlimb), skin (back of the rat), left brain, left eye and thigh muscle left side. There was a significant increase in TTW of the lung accompanied by pleural effusion after 48 h of oxygen exposure as expected in all exposed animals. There was a small increase in TTW of the paw only, and a small decrease or no change in other tissues after 24 and 48 h of exposure. We conclude that there is no evidence of systemic capillary dysfunction as measured by tissue water content after exposure to hyperoxia in a dosage causing pulmonary oedema. [source] Effect of Interictal Spikes on Single-Cell Firing Patterns in the HippocampusEPILEPSIA, Issue 4 2007Jun-Li Zhou Summary:,Purpose: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. Methods: We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. Results: IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. Conclusions: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner. [source] Mu opioid receptor modulation of somatodendritic dopamine overflow: GABAergic and glutamatergic mechanismsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2009V. I. Chefer Abstract Mu opioid receptor (MOR) regulation of somatodendritic dopamine neurotransmission in the ventral tegmental area (VTA) was investigated using conventional microdialysis in freely moving rats and mice. Reverse dialysis of the MOR agonist DAMGO (50 and 100 ,m) into the VTA of rats produced a concentration-dependent increase in dialysate dopamine concentrations. Basal dopamine overflow in the VTA was unaltered in mice lacking the MOR gene. However, basal ,-aminobutyric acid (GABA) overflow in these animals was significantly increased, whereas glutamate overflow was decreased. Intra-VTA perfusion of DAMGO into wild-type (WT) mice increased dopamine overflow. GABA concentrations were decreased, whereas glutamate concentrations in the VTA were unaltered. Consistent with the loss of MOR, no effect of DAMGO was observed in MOR knockout (KO) mice. These data provide the first direct demonstration of tonically active MOR systems in the VTA that regulate basal glutamatergic and GABAergic neurotransmission in this region. We hypothesize that increased GABAergic neurotransmission following constitutive deletion of MOR is due to the elimination of a tonic inhibitory influence of MOR on GABAergic neurons in the VTA, whereas decreased glutamatergic neurotransmission in MOR KO mice is a consequence of intensified GABA tone on glutamatergic neurons and/or terminals. As a consequence, somatodendritic dopamine release is unaltered. Furthermore, MOR KO mice do not exhibit the positive correlation between basal dopamine levels and the glutamate/GABA ratio observed in WT mice. Together, our findings indicate a critical role of VTA MOR in maintaining an intricate balance between excitatory and inhibitory inputs to dopaminergic neurons. [source] Functional interaction between the associative parietal cortex and hippocampal place cell firing in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Etienne Save Abstract The hippocampus and associative parietal cortex (APC) both contribute to spatial memory but the nature of their functional interaction remains unknown. To address this issue, we investigated the effects of APC lesions on hippocampal place cell firing in freely moving rats. Place cells were recorded from APC-lesioned and control rats as they performed a pellet-chasing task in a circular arena containing three object cues. During successive recording sessions, cue manipulations including object rotation in the absence of the rat and object removal in the presence of the rat were made to examine the control exerted by the objects or by non-visual intramaze cues on place field location, respectively. Object rotations resulted in equivalent field rotation for all cells in control rats. In contrast, a fraction of place fields in APC-lesioned rats did not rotate but remained stable relative to the room. Object removal produced different effects in APC-lesioned and control rats. In control rats, most place fields remained stable relative to the previous object rotation session, indicating that they were anchored to olfactory and/or idiothetic cues. In APC-lesioned rats, a majority of place fields shifted back to their initial, standard location, thus suggesting that they relied on uncontrolled background cues to maintain place field stability. These results provide strong evidence that the hippocampus and the APC cooperate in the formation of spatial memory and suggest that the APC is involved in elaboration of a hippocampal map based on proximal landmarks. [source] Conditional involvement of striatal serotonin3 receptors in the control of in vivo dopamine outflow in the rat striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Grégory Porras Abstract Serotonin3 (5-HT3) receptors can affect motor control through an interaction with the nigrostriatal dopamine (DA) neurons, but the neurochemical basis for this interaction remains controversial. In this study, using in vivo microdialysis, we assessed the hypothesis that 5-HT3 receptor-dependent control of striatal DA release is conditioned by the degree of DA and/or 5-HT neuron activity and the means of DA release (impulse-dependent vs. impulse-independent). The different DA-releasing effects of morphine (1 and 10 mg/kg), haloperidol (0.01 mg/kg), amphetamine (1 and 2.5 mg/kg), and cocaine (10 and 20 mg/kg) were studied in the striatum of freely moving rats administered selective 5-HT3 antagonists ondansetron (0.1 mg/kg) or MDL 72222 (0.03 mg/kg). Neither of the 5-HT3 antagonists modified basal DA release by itself. Pretreatment with ondansetron or MDL 72222 reduced the increase in striatal DA release induced by 10 mg/kg morphine but not by 1 mg/kg morphine, haloperidol, amphetamine or cocaine. The effect of 10 mg/kg morphine was also prevented by intrastriatal ondansetron (1 µm) administration. Reverse dialysis with ondansetron also reduced the increase in DA release induced by the combination of haloperidol and the 5-HT reuptake inhibitor citalopram (1 mg/kg). Considering the different DA and 5-HT-releasing properties of the drugs used, our results demonstrate that striatal 5-HT3 receptors control selectively the depolarization-dependent exocytosis of DA only when central DA and 5-HT tones are increased concomitantly. [source] Activation of histaminergic H3 receptors in the rat basolateral amygdala improves expression of fear memory and enhances acetylcholine releaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2002Iacopo Cangioli Abstract The basolateral amygdala (BLA) is involved in learning that certain environmental cues predict threatening events. Several studies have shown that manipulation of neurotransmission within the BLA affects the expression of memory after fear conditioning. We previously demonstrated that blockade of histaminergic H3 receptors decreased spontaneous release of acetylcholine (ACh) from the BLA of freely moving rats, and impaired retention of fear memory. In the present study, we examined the effect of activating H3 receptors within the BLA on both ACh release and expression of fear memory. Using the microdialysis technique in freely moving rats, we found that the histaminergic H3 agonists R-,-methylhistamine (RAMH) and immepip, directly administered into the BLA, augmented spontaneous release of ACh in a similar manner. Levels of ACh returned to baseline on perfusion with control medium. Rats receiving intra-BLA, bilateral injections of the H3 agonists at doses similar to those enhancing ACh spontaneous release, immediately after contextual fear conditioning, showed stronger memory for the context,footshock association, as demonstrated by longer freezing assessed at retention testing performed 72 h later. Post-training, bilateral injections of 15 ng oxotremorine also had a similar effect on memory retention, supporting the involvement of the cholinergic system. Thus, our results further support a physiological role for synaptically released histamine, that in addition to affecting cholinergic transmission in the amygdala, modulates consolidation of fear memories [source] Endogenous histamine in the medial septum,diagonal band complex increases the release of acetylcholine from the hippocampus: a dual-probe microdialysis study in the freely moving ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002Lucia Bacciottini Abstract The effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c-fos in the medial septum,diagonal band (MSA-DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA-DB neurons, we used the dual-probe microdialysis technique to apply drugs to the MSA-DB and record the induced effects in the projection area. Perfusion of MSA-DB with high-KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra-MSA-DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA-DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA-DB, increased the release of hippocampal ACh, whereas R-,-methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA-DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c-fos immunoreactivity were significantly more numerous in ciproxifan- or thioperamide-treated rats than in controls, although no colocalization of anti-c-fos and anti-ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus. [source] Histamine H3 receptor-mediated impairment of contextual fear conditioning and in-vivo inhibition of cholinergic transmission in the rat basolateral amygdalaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001M. Beatrice Passani Abstract We investigated the effects of agents acting at histamine receptors on both, spontaneous release of ACh from the basolateral amygdala (BLA) of freely moving rats, and fear conditioning. Extensive evidence suggests that the effects of histamine on cognition might be explained by the modulation of cholinergic systems. Using the microdialysis technique in freely moving rats, we demonstrated that perfusion of the BLA with histaminergic compounds modulates the spontaneous release of ACh. The addition of 100 mm KCl to the perfusion medium strongly stimulated ACh release, whereas, 0.5 µm tetrodotoxin (TTX) inhibited spontaneous ACh release by more than 50%. Histaminergic H3 antagonists (ciproxifan, clobenpropit and thioperamide), directly administered to the BLA, decreased ACh spontaneous release, an effect fully antagonized by the simultaneous perfusion of the BLA with cimetidine, an H2 antagonist. Local administration of cimetidine alone increased ACh spontaneous release slightly, but significantly. Conversely, the administration of H1 antagonists failed to alter ACh spontaneous release. Rats receiving intra-BLA, bilateral injections of the H3 antagonists at doses similar to those inhibiting ACh spontaneous release, immediately after contextual fear conditioning, showed memory consolidation impairment of contextual fear conditioning. Post-training, bilateral injections of 50 µg scopolamine also had an adverse effect on memory retention. These observations provide the first evidence that histamine receptors are involved in the modulation of cholinergic tone in the amygdala and in the consolidation of fear conditioning. [source] Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of ,2 -adrenergic and serotonin2C receptors: a comparison with citalopramEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2000M. J. Millan Abstract Mirtazapine displayed marked affinity for cloned, human ,2A -adrenergic (AR) receptors at which it blocked noradrenaline (NA)-induced stimulation of guanosine-5,-O-(3-[35S]thio)-triphosphate ([35S]-GTP,S) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5-HT)2C receptors at which it abolished 5-HT-induced phosphoinositide generation. Alpha2 -AR antagonist properties were revealed in vivo by blockade of UK-14,304-induced antinociception, while antagonist actions at 5-HT2C receptors were demonstrated by blockade of Ro 60 0175-induced penile erections and discriminative stimulus properties. Mirtazapine showed negligible affinity for 5-HT reuptake sites, in contrast to the selective 5-HT reuptake inhibitor, citalopram. In freely moving rats, in the dorsal hippocampus, frontal cortex (FCX), nucleus accumbens and striatum, citalopram increased dialysate levels of 5-HT, but not dopamine (DA) and NA. On the contrary, mirtazapine markedly elevated dialysate levels of NA and, in FCX, DA, whereas 5-HT was not affected. Citalopram inhibited the firing rate of serotonergic neurons in dorsal raphe nucleus, but not of dopaminergic neurons in the ventral tegmental area, nor adrenergic neurons in the locus coeruleus. Mirtazapine, in contrast, enhanced the firing rate of dopaminergic and adrenergic, but not serotonergic, neurons. Following 2 weeks administration, the facilitatory influence of mirtazapine upon dialysate levels of DA and NA versus 5-HT in FCX was maintained, and the influence of citalopram upon FCX levels of 5-HT versus DA and NA was also unchanged. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons. In conclusion, in contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission. These actions reflect antagonist properties at ,2A -AR and 5-HT2C receptors. [source] Daily jaw muscle activity in freely moving rats measured with radio-telemetryEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 1 2007Nobuhiko Kawai The jaw muscle activity of rats has been investigated for specific tasks. However, the daily jaw muscle use remains unclear. The purpose of the present study was to examine daily jaw muscle activity, and its variability over time, in the rat (n = 12) by the use of radio-telemetry. A telemetric device was implanted for the continuous recording of masseter muscle and digastric muscle activity. Daily muscle use was characterized by calculating the total time that each muscle was active (duty time), the number of bursts, and the average length of bursts. All parameters were estimated for activities exceeding various levels (5,90%) of the day's peak activity. Daily muscle use remained constant for 4 wk. At the low-activity level, the duty time and burst number of the digastric muscle were significantly (P < 0.01) higher than those of the masseter muscle, whereas the opposite was true at the high-activity level (P < 0.05). No significant intermuscular correlation was observed between the number of bursts of the masseter and digastric muscles, but the interindividual variation of both muscles changed, depending on the level of activation. These findings suggest that the masseter muscle and the digastric muscle show a differential active pattern, depending on the activity level. [source] Possible Contribution of Central Gamma-Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving RatsEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Yumi Takemoto Previous studies have shown that central administration of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co-varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone. [source] Hippocampal synaptic transmission and LTP in vivo are intact following bilateral vestibular deafferentation in the ratHIPPOCAMPUS, Issue 4 2010Yiwen Zheng Abstract Numerous studies in animals and humans have shown that damage to the vestibular system in the inner ear results in spatial memory deficits, presumably because areas of the brain such as the hippocampus require vestibular input to accurately represent the spatial environment. Consistent with this hypothesis, studies in animals have demonstrated that complete bilateral vestibular deafferentation (BVD) causes a disruption of place cell firing as well as theta activity. The aim of this study was to investigate whether BVD in rats affects baseline field potentials (field excitatory postsynaptic potentials and population spikes) and long-term potentiation (LTP) in CA1 and the dentate gyrus (DG) of awake freely moving rats up to 43 days post-BVD and of anesthetized rats at 7 months post-BVD. Compared to sham controls, BVD had no significant effect on either baseline field potentials or LTP in either condition. These results suggest that although BVD interferes with the encoding, consolidation, and/or retrieval of spatial memories and the function of place cells, these changes are not related to detectable in vivo decrements in basal synaptic transmission or LTP, at least in the investigated pathways. © 2009 Wiley-Liss, Inc. [source] A single application of MK801 causes symptoms of acute psychosis, deficits in spatial memory, and impairment of synaptic plasticity in ratsHIPPOCAMPUS, Issue 2 2008Denise Manahan-Vaughan Abstract Schizophrenia is mostly a progressive psychiatric illness. Although cognitive changes in chronic schizophrenia have been investigated, little is known about the consequences of a single psychotic episode on memory mechanisms and formation. We investigated changes in hippocampal long-term potentiation (LTP) and spatial memory in a rat model of an acute psychotic episode. Application of NMDA receptor antagonists, such as MK801 (dizolcilpine) in rats, have been shown to give rise to an acute and short-lasting behavioral state, which mirrors many symptoms of schizophrenia. Furthermore, NMDA antagonist-intake in humans elicits symptoms of schizophrenia such as hallucinations, delusions, and affective blunting. We therefore treated animals with a single systemic injection of MK801 (5 mg/kg). Increased stereotypy, locomotion, and ataxia were evident immediately after MK801-treatment, with effects disappearing within 24 h. MK801-treatment caused a disruption of prepulse inhibition of the acoustic startle reflex, 1 day but not 7 or 28 days after treatment. These effects were consistent with the occurrence of an acute psychotic episode. LTP was profoundly impaired in freely moving rats 7 days after MK801 application. Four weeks after treatment, a slight recovery of LTP was seen, however marked deficits in long-term spatial memory were evident. These data suggest that treatment with MK801 to generate an acute psychotic episode in rats, gives rise to grave disturbances in synaptic plasticity and is associated with lasting impairments with the ability to form spatial memory. © 2007 Wiley-Liss, Inc. [source] Comparison of spontaneous and septally driven hippocampal theta field and theta-related cellular activityHIPPOCAMPUS, Issue 1 2004Darren Scarlett Abstract Experiments were carried out for the purpose of comparing the electrophysiological properties of spontaneously occurring hippocampal theta field activity with those of theta-like field activity elicited by 5-Hz and 7-Hz electrical stimulation of the medial septum in urethane-anesthetized rats. Experiment 1 compared the amplitude and phase depth profiles for the three conditions of spontaneously occurring theta, theta elicited by 5-Hz medial septal stimulation, and theta elicited by 7-Hz medial septal stimulation. The results supported the conclusion that septally elicited theta field activity exhibited characteristics similar to those of spontaneously occurring theta field activity. Experiment 2 compared the discharge properties of hippocampal theta-related cellular discharges during spontaneous and septally elicited theta field activity. In contrast to the results of Experiment 1, the findings of Experiment 2 supported the conclusion that electrical stimulation of medial septal nuclei did not produce typical responses of hippocampal theta-related cellular activity. During spontaneously occurring field conditions, HPC theta-ON cells increased their discharge rates during spontaneous theta field activity, relative to LIA, and theta-OFF cells decreased (often to zero) their discharge rates during theta field activity relative to LIA. During septally elicited theta-like activity, phasic and tonic theta-ON cells decreased their discharge rates (some were totally inhibited), and most tonic theta-OFF cells increased their discharge rates (although two were totally inhibited). In addition, the discharges (albeit reduced) of the majority of both phasic and tonic theta-ON cells during septal driving became entrained to the stimulation pulses and thus exhibited rhythmicity and strong phase relations with the field activity. Furthermore, both cell types discharged near the positive peak of the septally elicited theta field activity during 5-Hz stimulation and near the negative peak during 7-Hz stimulation. The discharges of most tonic theta-OFF cells also became entrained to the stimulation pulses and exhibited similar phase relations to theta-ON cells during the 5-Hz and 7-Hz driving frequencies. Thus, based on cellular evidence, electrical stimulation of the medial septum activates the hippocampal neural circuitry involved in the generation of theta field activity in a nonphysiological manner. The findings of the present paper provide an explanation for why electrical stimulation of the medial septum in freely moving rats elicits a theta-like field activity that is dissociated from the normal behavioral correlates, in contrast to those elicited by stimulation of the posterior nucleus of the hypothalamus (Bland and Oddie. 2001. Behav Brain Res 127:119,136). © 2003 Wiley-Liss, Inc. [source] Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving ratsJOURNAL OF NEUROCHEMISTRY, Issue 1 2007H. Ronald Zielke Abstract Glucose is the primary carbon source to enter the adult brain for catabolic and anabolic reactions. Some studies suggest that astrocytes may metabolize glucose to lactate; the latter serving as a preferential substrate for neurons, especially during neuronal activation. The current study utilizes the aconitase inhibitor fluorocitrate to differentially inhibit oxidative metabolism in glial cells in vivo. Oxidative metabolism of 14C-lactate and14C-glucose was monitored in vivo using microdialysis and quantitating 14CO2 in the microdialysis eluate following pulse labeling of the interstitial glucose or lactate pool. After establishing a baseline oxidation rate, fluorocitrate was added to the perfusate. Neither lactate nor glucose oxidation was affected by 5 ,mol/L fluorocitrate. However, 20 and 100 ,mol/L fluorocitrate reduced lactate oxidation by 55 ± 20% and 68 ± 12%, respectively (p < 0.05 for both). Twenty and 100 ,mol/L fluorocitrate reduced 14C-glucose oxidation by 50 ± 14% (p < 0.05) and 24 ± 19% (ns), respectively. Addition of non-radioactive lactate to 14C-glucose plus fluorocitrate decreased 14C-glucose oxidation by an additional 29% and 38%, respectively. These results indicate that astrocytes oxidize about 50% of the interstitial lactate and about 35% of the glucose. By subtraction, neurons metabolize a maximum of 50% of the interstitial lactate and 65% of the interstitial glucose. [source] Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in ratsJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Marcello Solinas Abstract Although endogenous cannabinoid systems have been implicated in the modulation of the rewarding effects of abused drugs and food, little is known about the direct effects of endogenous ligands for cannabinoid receptors on brain reward processes. Here we show for the first time that the intravenous administration of anandamide, an endogenous ligand for cannabinoid receptors, and its longer-lasting synthetic analog methanandamide, increase the extracellular dopamine levels in the nucleus accumbens shell of awake, freely moving rats, an effect characteristic of most drugs abused by humans. Anandamide produced two distinctly different effects on dopamine levels: (1) a rapid, transient increase that was blocked by the cannabinoid CB1 receptor antagonist rimonabant, but not by the vanilloid VR1 receptor antagonist capsazepine, and was magnified and prolonged by the fatty acid amide hydrolase (FAAH) enzyme inhibitor, URB597; (2) a smaller delayed and long-lasting increase, not sensitive to CB1, VR1 or FAAH blockade. Both effects were blocked by infusing either tetrodotoxin (TTX, 1 µm) or calcium-free Ringer's solution through the microdialysis probe, demonstrating that they were dependent on the physiologic activation of dopaminergic neurotransmission. Thus, these results indicate that anandamide, through the activation of the mesolimbic dopaminergic system, participates in the signaling of brain reward processes. [source] Tissue Distribution, Autoradiography, and Metabolism of 4-(2,-Methoxyphenyl)-1-[2, -[N -2,-Pyridinyl)- p -[18F]Fluorobenzamido]ethyl]piperazine (p -[18F]MPPF), a New Serotonin 5-HT1A Antagonist for Positron Emission TomographyJOURNAL OF NEUROCHEMISTRY, Issue 2 2000An In Vivo Study in Rats The in vivo behavior of 4-(2,-methoxyphenyl)-1-[2,-[N -(2,-pyridinyl)- p -[18F]fluorobenzamido]ethyl]-piperazine (p -[18F]MPPF), a new serotonin 5-HT1A antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p -[18F]MPPF and in vitro 8-hydroxy-2-(di- n -[3H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p -[18F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT1A receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p -[18F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT1A specificity of p -[18F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT1A binding sites in the brain. [source] | |||||||||||||