Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression.
Kennett GA., Dourish CT., Curzon G.
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.