Effect of 5-HT1A receptor agonists in two models of anxiety after dorsal raphe injection.
The purpose of the present study was two-fold. Firstly, to present a more comprehensive analysis of the disinhibitory effects of 5-HT1A receptor agonists after discrete dorsal raphe (DRN) injections (Higgins et al. 1988). Secondly, the effects of the 5-HT1B receptor agonist CGS12066B and the 5-HT1B/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 micrograms), buspirone (0.04-0.2 microgram), ipsapirone (0.2 microgram) and gepirone (0.2-1 micrograms) 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-HT1B agonist CGS12066B (2.5 micrograms), but not the putative 5-HT1B/1C agonist mCPP (0.5-12.5 micrograms), increased SI under the HLU condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neuropharmacology, Glaxo Group Research Ltd., Ware, Herts, UK.
G A
GA
Higgins
B J
BJ
Jones
N R
NR
Oakley
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy*; D003220:Conflict, Psychological; D007267:Injections; D007398:Interpersonal Relations; D008297:Male; D008845:Microinjections; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011743:Pyrimidines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C052561:CGS 12066B; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C039979:gepirone