213 106 106 2 2 Guy A. Higgins Brian J. Jones Nigel R. Oakley Department of Neuropharmacology Glaxo Group Research Ltd. SG12 0DP Ware Herts UK Addiction Research Foundation 33 Russell Street M5S 2S1 Toronto Ontario Canada Smith-Kline Beecham Pharmaceuticals Coldharbour Road, The Pinnacles CM19 5AD Harlow Essex UK 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.
Psychopharmacology – Springer Journals
Published: Jun 1, 1992
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