The discriminative stimulus properties of the 5HT1 agonist RU24969

Using standard operant procedures, rats were trained to discriminate the 5-HT agonist RU24969 (0.5 mg/kg IP) from saline. Stable responding was established and tests of stimulus generalisation and stimulus antagonism were performed with a range of 5-HT receptor ligands. The RU24969 cue was selective as neither 5-HT receptor ligands MK212, DPAT, ipsapirone, GR38032F or the 5-HT releasing agent, fenfluramine nor yohimbine were able to substitute for RU24969 in tests of generalisation. However, TFMPP, CPP and, of particular interest, propranolol substituted for the RU24969 stimulus, although full substitution only occurred with doses that disrupted responding. The RU24969 stimulus was not antagonised by propranolol, metergoline, ritanserin or GR38032F. This pharmacological profile suggests that the RU24969 stimulus is mediated via a subtype of 5-HT1 sites different from 5-HT1A and that propranolol may be an agonist at this site.