Antidepressant-like activity of 5-HT1A agonists measured with the forced swim test.
This study examined the abilities of 5-hydroxytryptamine (5-HT) agonists with varying selectivity for different subtypes of 5-HT receptors to produce antidepressant-like behavioral effects in the forced swim test in rats. The 5-HT1A agonists 8-OH-DPAT (0.125-1.0 mg/kg, SC) and tandospirone (SM-3997) (5-20 mg/kg, SC) both produced dose-related decreases in immobility time following subchronic treatment in rats. These effects were similar to those of the tricyclic antidepressants imipramine (5-15 mg/kg) and desipramine (5-15 mg/kg). In addition, the 5-HT1A agonists, buspirone (20 mg/kg), gepirone (20 mg/kg) and ipsapirone (10 and 20 mg/kg) demonstrated antidepressant-like effects. Other groups of rats treated subchronically with each of the 5-HT1A agonists or antidepressants showed no increase in locomotor activity, so that general changes in activity could not account for the reduction of immobility time in the forced swim test. 5-HT agonists selective for other receptor subtypes, such as the 5-HT1B/1C agonist m-CPP (5 mg/kg) and the 5-HT2/1C agonist DOB (1 mg/kg), were not effective in this behavioral test. The benzodiazepine diazepam (5 mg/kg) also failed to reduce immobility time, suggesting that anxiolytic properties of 5-HT1A agonists did not mediate this behavioral effect. A common metabolite of some of the 5-HT1A agonists, 1-PP, was ineffective in reducing immobility time. The stimulant d-amphetamine (2 mg/kg) significantly reduced immobility time but also significantly increased locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Wieland
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S
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104.
Lucki
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I
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D013550:Swimming
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D003913:Dextroamphetamine