5-HT1C receptor-mediated phosphoinositide hydrolysis in the rat choroid plexus after chronic treatment with clozapine.
Chronic treatment with clozapine (14 days; 10 and 25 mg/kg/day) decreases 5-HT1C 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-HT1C receptors (measured by maximal stimulation of 5-HT1C receptor-mediated phosphoinositide hydrolysis) in relation to receptor changes in rat choroid plexus. Quantitative 5-HT1C receptor autoradiography indicated that chronic clozapine treatment decreased, in a dose-related manner, 5-HT1C receptor binding sites labeled by antagonist ([3H]mesulergine) and agonist ([125I](+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, [125I]DOI) radioligands. However, only the higher dose of clozapine decreased statistically significantly the maximal 5-HT1C receptor-mediated phosphoinositide hydrolysis response. Chronic administration of haloperidol (0.5 mg/kg/day) did not change any of the 5-HT1C receptor parameters. In conclusion, chronic clozapine treatment is able to modulate the function of 5-HT1C receptors. This further strengthens the possibility that 5-HT1C receptors may contribute to some of the atypical effects of clozapine.
Department of Pharmacology, University of Turku, Finland.
M
M
Kuoppamäki
E P
EP
Pälvimäki
E
E
Syvälahti
J
J
Hietala
D000662:Amphetamines / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology*; D004873:Ergolines / Q000493:pharmacokinetics; D006220:Haloperidol / Q000494:pharmacology; D006868:Hydrolysis; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics
D000662:Amphetamines; D004873:Ergolines; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D003024:Clozapine; D006220:Haloperidol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C031649:mesulergine