Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression

Eur J Pharmacol. 1987 Feb 24;134(3):265-74. doi: 10.1016/0014-2999(87)90357-8.

Abstract

Previous results have suggested that behavioural adaptation to restraint might be promoted by post-restraint stimulation of 5-HT1A receptors. Therefore, rats were restrained for 2 h and injected with vehicle or 60-1,000 micrograms/kg of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) s.c. Vehicle-treated restrained rats showed reduced locomotor activity and increased defaecation in an open field test the day after the end of restraint. A single injection of 250 or 1,000 micrograms/kg 8-OH-DPAT attenuated these effects. The above locomotor deficits were also attenuated by chronic pretreatment with the antidepressants desipramine and sertraline but not by a single treatment with desipramine or the benzodiazepine anxiolytic drugs chlordiazepoxide and diazepam; none of these treatments unambiguously reversed stress-induced increases in defaecation. Evidence suggests that the above action of 8-OH-DPAT is mediated by 5-HT1A receptors since it was antagonised by the 5-HT1A antagonist spiperone but not by the 5-HT2 antagonist ketanserin and was not mimicked by the 5-HT1B agonist RU 24969. However, the 5-HT1A agonists buspirone and TVXQ 7821 (ipsapirone) and the non-specific 5-HT agonist quipazine all possess similar properties to 8-OH-DPAT in this test. The results suggest that 5-HT1A agonists may have rapid antidepressant properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Antidepressive Agents / pharmacology*
  • Benzodiazepines
  • Buspirone
  • Depressive Disorder / physiopathology*
  • Disease Models, Animal
  • Drug Interactions
  • Indoles / pharmacology
  • Male
  • Motor Activity / drug effects
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Restraint, Physical
  • Serotonin / physiology*
  • Stress, Psychological / physiopathology
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Indoles
  • Pyrimidines
  • Tetrahydronaphthalenes
  • Benzodiazepines
  • 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole
  • Serotonin
  • ipsapirone
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Buspirone