MODE OF ACTION OF ANTIPSYCHOTIC-DRUGS - LESSONS FROM SIMPLER MODELS

The monoaminergic system of the pond snail Lymnaea stagnalis changed m arkedly following prolonged exposure to chlorpromazine (CPZ). HPLC-ED indicated that levels of serotonin (5-HT), but not those of dopamine, were significantly decreased (e.g., to less than 40% after 30 days of treatment with 1 mu M CPZ). Glyoxylate-induced fluorescence was depres sed to undetectable levels in selected subpopulations of 5-HT neurons. Performance of 5-HT-dependent motor behaviors was impaired, and a con siderably decreased firing activity was observed in affected 5-HT neur ons. The present results, in accord with past ones with haloperidol, s uggest that a previously overlooked mechanism of monoamine down-regula tion may contribute to effects of antipsychotic drugs.