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. Ho wever, its effect on steady state levels of monoamines is still in dis crepancy. In the present study, CPZ (4 mg/kg body weight) was administ ered intraperitoneally to adult Wistar rats chronically for 75 days an d the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytrypta mine (5-HT) were assayed in various brain regions by high performance liquid chromatography (HPLC). After the experimental period body and b rain 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 cor tex by 39% (p < 0.001), striatum-accumbens by 18% (p < 0.01), hippocam pus 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 c ompared to controls. The results suggest that chronic CPZ administrati on 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 mig ht be responsible for certain side effects seen in patients after chro nic CPZ treatment.