Home About us Contact
|
Home About us Contact | ||
|
|
||
Rotarod Test (rotarod + test)
Selected AbstractsPentylenetetrazol-induced Recurrent Seizures in Rat Pups: Time Course on Spatial Learning and Long-term EffectsEPILEPSIA, Issue 6 2002Li-Tung Huang Summary: ,Purpose: Recurrent seizures in infants are associated with a high incidence of neurocognitive deficits. Animal models have suggested that the immature brain is less vulnerable to seizure-induced injury than is that in adult animals. We studied the effects of recurrent neonatal seizures on cognitive tasks performed when the animals were in adolescence and adulthood. Methods: Seizures were induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for spatial memory by using the Morris water maze task. In adulthood, motor performance was examined by the Rotarod test, and activity level was assessed by the open field test. Seizure threshold was examined by inhalant flurothyl. To assess presence or absence of spontaneous seizures, rats were video recorded for 4 h/day for 10 consecutive days for the detection of spontaneous seizures. Finally, brains were examined for histologic evidence of injury with cresyl violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell layers of the hippocampus. Results: PTZ-treated rats showed significant spatial deficits in the Morris water maze at both P35 and P60. There were no differences in seizure threshold, motor balance, or activity level during the open field test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain showed no cell loss in either the control or experimental rats. PTZ-treated rats exhibited more Timm staining in the CA3 subfield. However, the control and experimental rats showed similar Timm staining within the supragranular zone. Conclusions: Our findings indicate that recurrent PTZ-induced seizures result in long-term cognitive deficits and morphologic changes in the developing brain. Furthermore, these cognitive deficits could be detected during pubescence. [source] Ethanol-induced elevation of 3,-hydroxy-5,-pregnan-20-one does not modulate motor incoordination in ratsALCOHOLISM, Issue 8 2004Rahul T. Khisti Background: Ethanol administration elevates the levels of GABAergic neuroactive steroids in brain and contributes to some of its behavioral actions. In the present study, we investigated whether such elevation of GABAergic neuroactive steroids contributes to the motor incoordinating effects of ethanol. Methods: Sprague-Dawley rats were administered ethanol (2 g/kg intraperitoneally) or saline, and the level of 3,-hydroxy-5,-pregnan-20-one (3,,5,-THP) was measured across time in cerebral cortex and in various brain regions at the peak time by radioimmunoassay. To study whether increases in GABAergic neuroactive steroids are responsible for the motor incoordinating actions of ethanol, rats were subjected to chemical (5,-reductase inhibitor, finasteride) and surgical (adrenalectomy) manipulations before receiving ethanol (2 g/kg intraperitoneally) injections. The rats were then subjected to different paradigms to evaluate motor impairment including the Majchrowicz motor intoxication rating scale, Rotarod test, and aerial righting reflex task at different time points. Results: The radioimmunoassay of 3,,5,-THP in different brain regions showed that ethanol increases 3,,5,-THP levels by 3- and 9-fold in cerebral cortex and hippocampus, respectively. There was no change in 3,,5,-THP levels in cerebellum and midbrain. The time course of 3,,5,-THP elevations in the cerebral cortex showed significant increases 20-min after ethanol injection with a peak at 60 min. In contrast, motor toxicity peaked between 5 and 10 min after ethanol injections and gradually decreased over time. Furthermore, adrenalectomy or pretreatment with finasteride (2 × 50 mg/kg, subcutaneously) did not reduce motor incoordinating effects of ethanol as assessed by the Majchrowicz intoxication rating score, Rotarod test, or aerial righting reflex task. Conclusions: Ethanol increases GABAergic neuroactive steroids in a time- and brain region-selective manner. The role of neuroactive steroids in alcohol action is specific for certain behaviors. Alcohol-induced deficits in motor coordination are not mediated by elevated neuroactive steroid biosynthesis. [source] Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l -DOPA-induced dyskinesiaJOURNAL OF NEUROCHEMISTRY, Issue 6 2003M. Lundblad Abstract We have examined the ability of KW-6002, an adenosine A2a antagonist, to modulate the dyskinetic effects of l -DOPA in 6-hydroxydopamine-lesioned rats. In animals rendered dyskinetic by a previous course of l -DOPA treatment, KW-6002 did not elicit any abnormal involuntary movements on its own, but failed to reduce the severity of dyskinesia when coadministered with l -DOPA. A second experiment was undertaken in order to study the effects of KW-6002 in l -DOPA-naive rats. Thirty-five animals were allotted to four groups to receive a 21-day treatment with: (i) KW-6002 (10 mg/kg/day); (ii) l -DOPA (6 mg/kg/day) i.p.; (iii) KW-6002 plus l -DOPA (same doses as above) or (iv) vehicle. Chronic treatment with KW-6002-only produced a significant relief of motor disability in the rotarod test in the absence of any abnormal involuntary movements. Combined treatment with l -DOPA and KW-6002 improved rotarod performance to a significantly higher degree than did each of the two drugs alone. However, this combined treatment induced dyskinesia to about the same degree as did l -DOPA alone. In situ hybridization histochemistry showed that KW-6002 treatment alone caused an approximately 20% reduction in the striatal levels of preproenkephalin mRNA, whereas neither the coadministration of KW-6002 and l -DOPA nor l -DOPA alone significantly altered the expression of this transcript in the dopamine-denervated striatum. Either alone or in combination with l -DOPA, KW-6002 did not have any modulatory effect on prodynorphin mRNA expression or FosB/,FosB-like immunoreactivity in the dopamine-denervated striatum. These results show that monotreatment with an adenosine A2a receptor antagonist can relieve motor disability without inducing behavioural and cellular signs of dyskinesia in rats with 6-hydroxydopamine lesions. Cotreatment with KW-6002 and l -DOPA potentiates the therapeutic effect but not the dyskinesiogenic potential of the latter drug. [source] Neuroprotective effect of HT008-1, a prescription of traditional Korean medicine, on transient focal cerebral ischemia model in ratsPHYTOTHERAPY RESEARCH, Issue 8 2010Youngmin Bu Abstract HT008-1 is one of the prescriptions used in Traditional Korean Medicine for the treatment of mental and physical weakness. It is composed of Panax ginseng, Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis, which have been reported to have various pharmacological effects on the central nervous system. The study investigated whether HT008-1 has neuroprotective effects in a focal cerebral ischemia rat model. Stroke was induced in rats by 2,h of middle cerebral artery occlusion (MCAo) followed by 22,h of reperfusion. HT008-1 (30, 100 and 300,mg/kg) and the component herbs (300,mg/kg) were administered orally twice at 0 and 2,h after ischemia. Oral administration of 300,mg/kg HT008-1 reduced brain infarction by 45.7%, prolonged the latency time by 24.8% in the rotarod test, and enhanced the score by 17.0% in the balance beam test. Only P. ginseng and S. baicalensis showed protective effects, and HT008-1 showed a greater effect than its component herbs. HT008-1 down-regulated the COX-2 and OX-42 expression in the penumbra region. In conclusion, the results show that HT008-1 may be effective in a rat stroke model by an antiinflammatory mechanism and may improve sensory-motor function by reducing damage in the cortex and caudoputamen. Copyright © 2010 John Wiley & Sons, Ltd. [source] Synthesis and Anticonvulsant Activity of N -(2-Hydroxy-ethyl)amide DerivativesARCHIV DER PHARMAZIE, Issue 1 2009Li-Ping Guan Abstract A series novel of N -(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N -(2-hydroxyethyl)decanamide 1g, N -(2-hydroxyethyl)palmitamide 1l, and N -(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine. [source] | ||||||||||