Sodium valproate induced alterations in monoamine levels in different regions of the rat brain.
Sodium valproate is a well established anticonvulsant drug but its exact mode of action is not yet clear. With a view to find out whether the mechanism of action of sodium valproate is mediated by alteration in monoamine levels, apart from GABA, in brain, sodium valproate (200 mg/kg body wt) was administered i.p. to male adult Wistar rats for 45 days. The levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed in different brain regions using high performance liquid chromatographic (HPLC) method. It was noted that at the end of the experimental period there was no change in body or brain weight nor were there any neurological deficits as a result of sodium valproate administration. However, after administration of sodium valproate there was a significant increase in norepinephrine levels in hippocampus (P < 0.01) and brainstem (P < 0.01) while a significant decrease was noted in hypothalamus (P < 0.001). Dopamine levels were significantly increased in motor cortex (P < 0.01), hippocampus (P < 0.01) and hypothalamus (P < 0.001). Serotonin levels were significantly increased in striatum-accumbens and brain stem (P < 0.001). However a marginal increase was also observed in motor cortex and hippocampus. 5-HT levels were significantly decreased in hypothalamus (P < 0.001) and cerebellum (P < 0.01). The present findings suggest the possibility that the anticonvulsant effect of sodium valproate could be due to alterations in monoamine levels apart from its action on GABA, which would indicate also the efficacy of this drug in different types of seizures.
Baf
M H
MH
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Subhash
M N
MN
Lakshmana
K M
KM
Rao
B S
BS
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
D015306:Biogenic Monoamines; D012701:Serotonin; D014635:Valproic Acid; D004298:Dopamine; D009638:Norepinephrine