213 100 100 3 3 François Jenck Chris L. E. Broekkamp Anton M. L. Van Delft CNS Pharmacology Department Organon International P.O. Box 20 NL-5340 BH OSS The Netherlands Pharmaceutical Research Department- 72/148 - Hoffmann-La Roche Ltd. CH-4002 Basel Switzerland Abstract The functional role of brain 5-HT and 5-HT receptor subtypes in periaqueductal gray (PAG) induced aversion has been investigated in rats. Antiaversive effects were found with the serotonin agonists TFMPP, mCPP and DOI but not with RU 24969 which was found to facilitate PAG aversion. The first three serotonin agonists share potent 5-HT 1C activity while RU 24969 differs with a high 5-HT 1A activity. Proaversive effects were found with the mixed 5-HT 1C /5-HT 2 antagonists cyproheptadine and ritanserin; this effect was already reported for the mixed 5-HT 1C /5-HT 2 antagonists metergoline and mianserin and is opposite to the effects of the selective 5-HT 2 antagonists ketanserin, pirenperone, trazodone and spiperone. The antiaversive effects of mCPP (1 mg/kg) could be prevented by pretreatment of the animals with mianserin (1 and 10 mg/kg). These results suggest that 5-HT 1C receptors play an important role in the serotonergic control of PAG aversion. 5-HT 1C receptor activation seems to mediate antiaversive effects whereas acute 5-HT 1C receptor blockade appears to facilitate PAG aversion. Functional interactions take place between several receptor types in the in vivo control of PAG aversion, where 5-HT 1C receptors appear to play a predominant function.
Psychopharmacology – Springer Journals
Published: Mar 1, 1990
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