Mode of action of antipsychotic drugs: lessons from simpler models.

The monoaminergic system of the pond snail Lymnaea stagnalis changed markedly 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 microM CPZ). Glyoxylate-induced fluorescence was depressed to undetectable levels in selected subpopulations of 5-HT neurons. Performance of 5-HT-dependent motor behaviors was impaired, and a considerably decreased firing activity was observed in affected 5-HT neurons. The present results, in accord with past ones with haloperidol, suggest that a previously overlooked mechanism of monoamine down-regulation may contribute to affects of antipsychotic drugs.