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Awake Rats (awake + rat)
Selected AbstractsECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological ConsiderationsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2003Peter Ericsson They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1,2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 ,l/hr the recovery of submucosal histamine was 49%, at 34 ,l/hr the recovery increased to 83%. At a perfusion rate below 20 ,l/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0,3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization. [source] Long-term synaptic depression in the adult entorhinal cortex in vivoHIPPOCAMPUS, Issue 7 2003Raby Bouras Abstract The piriform cortex provides a major input to the entorhinal cortex. Mechanisms of long-term depression (LTD) of synaptic transmission in this pathway may affect olfactory and mnemonic processing. We have investigated stimulation parameters for the induction of homosynaptic LTD and depotentiation in this pathway using evoked synaptic field potential recordings in the awake rat. In this study, 15 min of 1-Hz stimulation induced a transient (<5 min) depression of evoked responses but did not induce LTD or depotentiation. To determine whether inhibitory and/or facilitatory mechanisms contribute to LTD induction, repetitive delivery of pairs of stimulation pulses was also assessed. Repetitive paired-pulse stimulation with a 10-ms interval between pulses, which activates inhibitory mechanisms during the second response, did not reliably induce LTD. However, repetitive paired-pulse stimulation using a 30-ms interval, which evokes marked paired-pulse facilitation, resulted in synaptic depression that lasted ,1 day, and which was reversible by tetanization. The selective induction of LTD by stimulation that evokes paired-pulse facilitation suggests that strong synaptic activation is required for LTD induction. The N -methyl- D -aspartate (NMDA) receptor antagonist MK-801 (0.1 mg/kg) blocked the induction of LTD, indicating that NMDA receptor activation is required for LTD induction in this pathway. These results indicate that LTD in piriform cortex inputs to the entorhinal cortex in the awake rat is effectively induced by strong repetitive synaptic stimulation, and that this form of LTD is dependent on activation of NMDA receptors. © 2003 Wiley-Liss, Inc. [source] Melatonin disrupts circadian rhythms of glutamate and GABA in the neostriatum of the awake rat: a microdialysis studyJOURNAL OF PINEAL RESEARCH, Issue 4 2000B. Marquez de Prado The purpose of this study was to investigate possible circadian changes in extracellular concentrations of glutamate (GLU) and ,-aminobutyric acid (GABA), and the influence of melatonin on the levels of these neurotransmitters in the neostriatum of awake rats using in vivo microdialysis. At the same time, the concentrations of the amino acids taurine (TAU), glutamine (GLN) and arginine (ARG), as well as dopamine (DA) and its metabolites 3, 4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA), were measured in the extracellular fluid. When dialysates were collected over a 24-hr period (6 hr dark, 12 hr light, 6 hr dark), both GLU and GABA, without the infusion of melatonin, exhibited statistically significant rhythms, with higher levels of these constituents during the dark and lower levels during the day. Perfusion with melatonin (for 19 consecutive hours) prevented the daytime reductions in both GLU and GABA. Of the amino acids measured in the dialysates collected from the neostriatum of non-perfused rats, only ARG exhibited a significant change during the light:dark cycle; again, lowest concentrations were measured during the day. While melatonin perfusion did not statistically significantly influence neostriatal levels of TAU and ARG, GLN levels continued to drop during the infusion of the indoleamine. Dialysate concentrations of DA, DOPAC and HVA exhibited circadian rhythms which were not influenced by melatonin perfusion. The findings indicate there are differential effects of melatonin on extracellular neurotransmitter concentrations in the neostriatum of the awake rat. The results also suggest that the day:night variations in GLU and GABA may relate to daily changes in endogenous melatonin production, while DA and its metabolites are minimally influenced by this secretory product. [source] Sublinear summation of afferent inputs to the nucleus accumbens in the awake ratTHE JOURNAL OF PHYSIOLOGY, Issue 8 2009John A. Wolf The mechanisms by which the nucleus accumbens integrates afferent input from limbic and cortical structures have been influential in the development of models of psychiatric disorders such as schizophrenia. Previous studies of the response of nucleus accumbens (Nacb) cells to the stimulation of afferent inputs from hippocampus (HC) and prefrontal cortex (PFC) have demonstrated that PFC throughput can be modulated by preceding HC input. Examination of the post-synaptic potential size has suggested, however, that summation of these inputs is sublinear. All studies to date examining Nacb integration of inputs via stimulation of afferents have been performed in the anaesthetized rat. The present experiments compare the response of Nacb cells to different combinations of PFC and HC stimulation in awake and isoflurane-anaesthetized rats that were chronically implanted with both stimulating and recording electrodes. The results of these experiments suggest that summation of afferent input in the Nacb of the awake rat is predominantly sublinear, with only a minority of neurons demonstrating modulation of PFC inputs by the HC in the awake or the anaesthetized animal. The response profile of many cells changed during anaesthesia when compared to the awake condition, and on average showed suppression to PFC input 50 and 150 ms following HC stimulation while under deep isoflurane anaesthesia. These results suggest that sublinear integration of afferent input from the PFC and HC is the dominant mode of integration of Nacb cells in the awake animal, which has implications for corticostriatal models of psychiatric dysfunction. [source] Rat hippocampal theta rhythm during sensory mismatchHIPPOCAMPUS, Issue 4 2009D. Zou Abstract It has been suggested that sensory mismatch induces motion sickness, but its neural mechanisms remain unclear. To investigate this issue, theta waves in the hippocampal formation (HF) were studied during sensory mismatch by backward translocation in awake rats. A monopolar electrode was implanted into the dentate gyrus in the HF, from which local field potentials were recorded. The rats were placed on a treadmill affixed to a motion stage translocated along a figure 8-shaped track. The rats were trained to run forward on the treadmill at the same speed as that of forward translocation of the motion stage (a forward condition) before the experimental (recording) sessions. In the experimental sessions, the rats were initially tested in the forward condition, and then tested in a backward (mismatch) condition, in which the motion stage was turned around by 180° before translocation. That is, the rats were moved backward by translocation of the stage although the rats ran forward on the treadmill. The theta (6,9 Hz) power was significantly increased in the backward condition compared with the forward condition. However, the theta power gradually decreased by repeated testing in the backward condition. Furthermore, backward translocation of the stage without locomotion did not increase theta power. These results suggest that the HF might function as a comparator to detect sensory mismatch, and that alteration in HF theta activity might induce motion sickness. © 2008 Wiley-Liss, Inc. [source] Melatonin disrupts circadian rhythms of glutamate and GABA in the neostriatum of the awake rat: a microdialysis studyJOURNAL OF PINEAL RESEARCH, Issue 4 2000B. Marquez de Prado The purpose of this study was to investigate possible circadian changes in extracellular concentrations of glutamate (GLU) and ,-aminobutyric acid (GABA), and the influence of melatonin on the levels of these neurotransmitters in the neostriatum of awake rats using in vivo microdialysis. At the same time, the concentrations of the amino acids taurine (TAU), glutamine (GLN) and arginine (ARG), as well as dopamine (DA) and its metabolites 3, 4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA), were measured in the extracellular fluid. When dialysates were collected over a 24-hr period (6 hr dark, 12 hr light, 6 hr dark), both GLU and GABA, without the infusion of melatonin, exhibited statistically significant rhythms, with higher levels of these constituents during the dark and lower levels during the day. Perfusion with melatonin (for 19 consecutive hours) prevented the daytime reductions in both GLU and GABA. Of the amino acids measured in the dialysates collected from the neostriatum of non-perfused rats, only ARG exhibited a significant change during the light:dark cycle; again, lowest concentrations were measured during the day. While melatonin perfusion did not statistically significantly influence neostriatal levels of TAU and ARG, GLN levels continued to drop during the infusion of the indoleamine. Dialysate concentrations of DA, DOPAC and HVA exhibited circadian rhythms which were not influenced by melatonin perfusion. The findings indicate there are differential effects of melatonin on extracellular neurotransmitter concentrations in the neostriatum of the awake rat. The results also suggest that the day:night variations in GLU and GABA may relate to daily changes in endogenous melatonin production, while DA and its metabolites are minimally influenced by this secretory product. [source] Disparity Between Tonic and Phasic Ethanol-Induced Dopamine Increases in the Nucleus Accumbens of RatsALCOHOLISM, Issue 7 2009Donita L. Robinson Background:, Dopamine concentrations in the nucleus accumbens fluctuate on phasic (subsecond) and tonic (over minutes) timescales in awake rats. Acute ethanol increases tonic concentrations of dopamine, but its effect on subsecond dopamine transients has not been fully explored. Methods:, We measured tonic and phasic dopamine fluctuations in the nucleus accumbens of rats in response to ethanol (within-subject cumulative dosing, 0.125 to 2 g/kg, i.v.). Results:, Microdialysis samples yielded significant tonic increases in dopamine concentrations at 1 to 2 g/kg ethanol in each rat, while repeated saline infusions had no effect. When monitored with fast scan cyclic voltammetry, ethanol increased the frequency of dopamine transients in 6 of 16 recording sites, in contrast to the uniform effect of ethanol as measured with microdialysis. In the remaining 10 recording sites that were unresponsive to ethanol, dopamine transients either decreased in frequency or were unaffected by cumulative ethanol infusions, patterns also observed during repeated saline infusions. The responsiveness of particular recording sites to ethanol was not correlated with either core versus shell placement of the electrodes or the basal rate of dopamine transients. Importantly, the phasic response pattern to a single dose of ethanol at a particular site was qualitatively reproduced when a second dose of ethanol was administered, suggesting that the variable between-site effects reflected specific pharmacology at that recording site. Conclusions:, These data demonstrate that the relatively uniform dopamine concentrations obtained with microdialysis can mask a dramatic heterogeneity of phasic dopamine release within the accumbens. [source] ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological ConsiderationsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2003Peter Ericsson They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1,2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 ,l/hr the recovery of submucosal histamine was 49%, at 34 ,l/hr the recovery increased to 83%. At a perfusion rate below 20 ,l/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0,3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization. [source] Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRIBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008C-L Chin Background and purpose: Activation of cannabinoid CB1 and/or CB2 receptors mediates analgesic effects across a broad spectrum of preclinical pain models. Selective activation of CB2 receptors may produce analgesia without the undesirable psychotropic side effects associated with modulation of CB1 receptors. To address selectivity in vivo, we describe non-invasive, non-ionizing, functional data that distinguish CB1 from CB2 receptor neural activity using pharmacological MRI (phMRI) in awake rats. Experimental approach: Using a high field (7 T) MRI scanner, we examined and quantified the effects of non-selective CB1/CB2 (A-834735) and selective CB2 (AM1241) agonists on neural activity in awake rats. Pharmacological specificity was determined using selective CB1 (rimonabant) or CB2 (AM630) antagonists. Behavioural studies, plasma and brain exposures were used as benchmarks for activity in vivo. Key results: The non-selective CB1/CB2 agonist produced a dose-related, region-specific activation of brain structures that agrees well with published autoradiographic CB1 receptor density binding maps. Pretreatment with a CB1 antagonist but not with a CB2 antagonist, abolished these activation patterns, suggesting an effect mediated by CB1 receptors alone. In contrast, no significant changes in brain activity were found with relevant doses of the CB2 selective agonist. Conclusion and implications: These results provide the first clear evidence for quantifying in vivo functional selectivity between CB1 and CB2 receptors using phMRI. Further, as the presence of CB2 receptors in the brain remains controversial, our data suggest that if CB2 receptors are expressed, they are not functional under normal physiological conditions. British Journal of Pharmacology (2008) 153, 367,379; doi:10.1038/sj.bjp.0707506; published online 29 October 2007 [source] Spinal amino acid release and repeated withdrawal in spinal morphine tolerant ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Takae Ibuki We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance. Rats received lumbar intrathecal (IT) infusion of morphine (IT-M: 20 nmol ,l,1 h,1) or saline (IT-S: 1 ,l h,1) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP-N: 0.6 mg kg,1) or saline (IP-S: 3 ml kg,1) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured. Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine+IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine+i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups. For the IT-M+IP-N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3-day infusion interval. No change in basal resting release was noted for any other treatment. Evoked release (after i.p. naloxone) in IT-M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups. The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection. The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance. British Journal of Pharmacology (2003) 138, 689,697. doi:10.1038/sj.bjp.0705102 [source] | |||||||||||||