Effect of 5-HT1A receptor agonists in two models of anxiety after dorsal raphe injection

Psychopharmacology (Berl). 1992;106(2):261-7. doi: 10.1007/BF02801982.

Abstract

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)

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Animals
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / drug therapy*
  • Conflict, Psychological
  • Injections
  • Interpersonal Relations
  • Male
  • Microinjections
  • Piperazines / administration & dosage
  • Piperazines / pharmacology
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacology
  • Quinoxalines / administration & dosage
  • Quinoxalines / pharmacology
  • Raphe Nuclei
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Anti-Anxiety Agents
  • Piperazines
  • Pyrimidines
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • CGS 12066B
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • gepirone