Serotonin depletion after prolonged chlorpromazine treatment in a simpler model system.
1. Prolonged exposure of the pond snail Lymnaea stagnalis to micromolar concentrations of chlorpromazine (CPZ) results in marked changes in the serotonin (5-HT) content of the central nervous system. 2. High-performance liquid chromatography with electrochemical detection indicates 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 microM CPZ in the bathing water). 3. Glyoxylate-induced fluorescence was depressed to undetectable 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 haloperidol, suggest that previously overlooked mechanisms of monoamine downregulation may contribute to long-term effects of antipsychotic drugs.
Croll
R P
RP
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada. roger.croll@dal.ca
Baker
M W
MW
Khabarova
M
M
Voronezhskaya
E E
EE
Sakharov
D A
DA
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D008195:Lymnaea / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
D018492:Dopamine Antagonists; D012701:Serotonin; D002746:Chlorpromazine