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.
Baker
M W
MW
Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
Croll
R P
RP
Dyakonova
V
V
Khabarova
M
M
Sakharov
D A
DA
Voronezhskaya
E
E
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D015536:Down-Regulation; D008195:Lymnaea / Q000187:drug effects* / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism
D014150:Antipsychotic Agents; D015306:Biogenic Monoamines; D018492:Dopamine Antagonists; D012701:Serotonin; D002746:Chlorpromazine; D004298:Dopamine