Abstract
Chronic treatment with clozapine (14 days; 10 and 25 mg/kg/day) decreases 5-HT 1C receptor density but not affinity in rat choroid plexus measured with [ 3H]mesulergine. We now report the effects of the same clozapine treatment regimens on the function of 5-HT 1C receptors (measured by maximal stimulation of 5-HT 1C receptor-mediated phosphoinositide hydrolysis) in relation to receptor changes in rat choroid plexus. Quantitative 5-HT 1C receptor autoradiography indicated that chronic clozapine treatment decreased, in a dose-related manner, 5-HT 1C receptor binding sites labeled by antagonist ([ 3H]mesulergine) and agonist ( [ 125 I](±)-1-(2,5- dimethoxy-4- iodophenyl)-2- aminopropane, [ 125 I] DOI ) radioligands. However, only the higher dose of clozapine decreased statistically significantly the maximal 5-HT 1C receptor-mediated phosphoinositide hydrolysis response. Chronic administration of haloperidol (0.5 mg/kg/day) did not change any of the 5-HT 1C receptor parameters. In conclusion, chronic clozapine treatment is able to modulate the function of 5-HT 1C receptors. This further strengthens the possibility that 5-HT 1C receptors may contribute to some of the atypical effects of clozapine.
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