Effects of ritanserin on haloperidol-induced dopamine (D2) receptor up-regulation in the rat.
Rats were treated with vehicle, ritanserin (5 mg/kg, i.p.), haloperidol (1 mg/kg, i.p.) or both ritanserin and haloperidol for 19 days to determine whether chronic administration of the serotonin (5HT2) antagonist ritanserin affects D2 receptor up-regulation produced by haloperidol. Brain sections were prepared for D2 and 5HT2 receptor autoradiography with [3H]spiperone and [3H]ketanserin, respectively. Ritanserin significantly reduced 5HT2 receptors to 80% of vehicle in the sulcal area of the frontal cortex but had no effect on D2 receptors. Haloperidol significantly increased striatal and n. accumbens D2 receptors with no effect on 5HT2 receptors. In ritanserin/haloperidol-treated rats, D2 receptors were significantly increased along with significant decreases in 5HT2 receptors of the frontal cortex. These results suggest 5HT2 receptor antagonism by ritanserin does not significantly affect D2 receptor up-regulation produced by haloperidol.
Szczepanik
A M
AM
Neuroscience Research, Hoechst Marion Roussel, Inc., Bridgewater, NJ 08807-0800, USA.
Wilmot
C A
CA
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology; D001345:Autoradiography; D002540:Cerebral Cortex / Q000737:chemistry; D003024:Clozapine / Q000378:metabolism / Q000494:pharmacology; D003342:Corpus Striatum / Q000737:chemistry; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006220:Haloperidol / Q000378:metabolism / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D009714:Nucleus Accumbens / Q000737:chemistry; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D016713:Ritanserin / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011804:Quinolines; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D016713:Ritanserin; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; D003024:Clozapine; D006220:Haloperidol