SEROTONIN DEPLETION AFTER PROLONGED CHLORPROMAZINE TREATMENT IN A SIMPLER MODEL SYSTEM

1. Prolonged exposure of the pond snail Lymnaea stagnalis to micromola r concentrations of chlorpromazine (CPZ) results in marked changes in the serotonin (5-HT) content of the central nervous system. 2. High-pe rformance liquid chromatography with electrochemical detection indicat es that levels of 5-HT, but not those of dihydroxyphenyl-alanine (DOPA ), dopamine or norepinephrine, were significantly decreased (e.g., to less than 40% of normal after 30 days of exposure to 1 mu M CPZ in the bathing water). 3. Glyoxylate-induced fluorescence was depressed to u ndetectable levels in central, serotonergic neurons. 4. Performance of 5 HT-dependent motor behaviors was impaired. 5. The present results, in accord with earlier studies on the effects of chronic exposure to h aloperidol, suggest that previously overlooked mechanisms of monoamine downregulation may contribute to long-term effects of antipsychotic d rugs. (C) 1997 Elsevier Science Inc.