Discriminative stimulus properties of indorenate in a conditioned taste aversion paradigm

Indorenate (5-methoxytryptamine beta -methylcarboxylate, INDO) is a seroton in (5-hydroxytryptamine, 5-HT) agonist that has affinity for 5- HT1A/1B/2C receptors. It possesses anxiolytic and antihypertensive actions mediated by 5-HT1A receptors and anorectic activity mediated by 5-HT2C/1B receptors. T his study examined whether INDO may exert discriminative control using a co nditioned taste aversion (CTA) paradigm, and whether differential participa tion of 5-HT receptor subtypes may be involved in its cue. Male Wistar rats trained to drink their daily water in a 30-min period were trained to disc riminate INDO from saline. One group received the intraperitoneal administr ation of INDO (10.0 mg/kg) before saccharin-LiCl pairings; on alternate day s, rats received saline before the saccharin-saline pairings (Group D+S-). The other group had the contingencies reversed (i.e., the administration of INDO preceded saccharin-saline pairings: Group D-S+). In two-bottle genera lization tests (one bottle containing saccharin, the other plain water), th e preference for saccharin was evaluated after different doses of INDO, [H- 3]-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) (5-HT1A), buspirone ( 5-HT1A), RU24969 (5-HT1A/1B), TFMPP (5-HT1B/2C), MK212 (5-HT2C), alpha -Me- 5-HT (5-HT2C/2A), 2-Me-5-HT (5-HT3) and cisapride (5-HT4). The results show ed that INDO, RU24969, TFMPP, alpha -Me-5-HT and MK 212 produced a dose-dep endent generalization; 8-OH-DPAT and buspirone produced only partial genera lization, while 2-Me-5-HT and cisapride did not produce generalization. The results indicate that INDO administration may exert discriminative control over saccharin preference mediated mainly by 5-HT1B/2C receptors, but with an important contribution of 5-HT1A receptors. (C) 2001 Elsevier Science I nc. All rights reserved.