Effect of 5-HT_1A receptor agonists in two models of anxiety after dorsal raphe injection

Abstract

The purpose of the present study was two-fold. Firstly, to present a more comprehensive analysis of the disinhibitory effects of 5-HT_1A receptor agonists after discrete dorsal raphe (DRN) injections (Higgins et al. 1988). Secondly, the effects of the 5-HT_1B receptor agonist CGS12066B and the 5-HT_1B/1C agonist mCPP were examined following injection into this nucleus. The increases in social interaction (SI) induced by intra-raphe injections of 8-OH DPAT (0.02–1 μg), buspirone (0.04–0.2 μg), ipsapirone (0.2 μg) and gepirone (0.2–1 μg) under a high light unfamiliar paradigm (HLU) were typically due to increased bout frequency, duration and a higher incidence of sniff, follow, allogroom behaviour. These increases were qualitatively similar to those seen in control animals tested under low light/familiar (LLF) conditions, thus supporting the belief that the drug-induced increases in SI reflected decreases in anxiety. Furthermore, at doses effective under the HLU condition, 8-OH DPAT, buspirone and gepirone failed to modify SI under conditions of minimal suppression (LLF paradigm). At doses which significantly increased punished responding in a water-lick conflict test 8-OH DPAT, ipsapirone and gepirone tended to also increase unpunished rates of drinking. However, in drug untreated rats, prior habituation to the test apparatus also increased unpunished drinking, suggesting some neophobia-induced suppression. At a comparatively high dose, the 5-HT_1B agonist CGS12066B (2.5 μg), but not the putative 5-HT_1B/1c agonist mCPP (0.5–12.5 μg), increased SI under the HLU condition. Considered along-side the other compounds described in this report, the relative potency of CGS12066B may be reflective of a 5-HT_1A receptor interaction. Together, these data support the proposal that the DRN is an important site through wich 5-HT_1A receptor agonists express their anxiolytic actions.