The effect of chronic chlorpromazine administration on monoamine levels in various regions of rat brain.
The neuroleptic drug, chlorpromazine (CPZ) has been shown to exert its antipsychotic effect by blocking post synaptic dopamine receptors. However, its effect on steady state levels of monoamines is still in discrepancy. In the present study, CPZ (4 mg/kg body weight) was administered intraperitoneally to adult Wistar rats chronically for 75 days and the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) were assayed in various brain regions by high performance liquid chromatography (HPLC). After the experimental period body and brain weights were not statistically different from controls. NE and 5-HT levels were increased only in hippocampus by 15% (p < 0.01) and 16% (p < 0.01) respectively. DA levels were consistently increased in cortex by 39% (p < 0.001), striatum-accumbens by 18% (p < 0.01), hippocampus by 27% (p < 0.01), hypothalamus by 34% (p < 0.001), cerebellum by 36% (p < 0.001) and brainstem by 40% (p < 0.001) in CPZ treated rats compared to controls. The results suggest that chronic CPZ administration increases DA levels in almost all regions of brain and reflect the ability of CPZ to preferentially interfere with synaptic transmission mediated by DA in brain. It also suggests that this increase in DA might be responsible for certain side effects seen in patients after chronic CPZ treatment.
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; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D012701:Serotonin; D002746:Chlorpromazine; D004298:Dopamine; D009638:Norepinephrine