caa a22 4500 465738222 CHVBK 20180323111801.0 cr unu---uuuuu 170327e19900801xx s 000 0 eng 10.1007/BF02244228 doi (NATIONALLICENCE)springer-10.1007/BF02244228 Antidepressant-like activity of 5-HT1A agonists measured with the forced swim test [Elektronische Daten] [Scott Wieland, Irwin Lucki] 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 agonistm-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 stimulantd-amphetamine (2 mg/kg) significantly reduced immobility time but also significantly increased locomotor activity. Pretreatment with the 5-HT synthesis inhibitor PCPA alone did not alter immobility time, and did not alter the antidepressant-like effects of 8-OH-DPAT or tandospirone, suggesting that the 5-HT1A agonists are producing their antidepressant-like effects through postsynaptic 5-HT1A receptors. These results suggest that 5-HT1A agonists may have antidepressant efficacy and act as a novel class of antidepressant drug. Springer-Verlag, 1990 Antidepressants nationallicence 5-Hydroxytryptamine nationallicence 5-HT1A agonists nationallicence Anxiolytics nationallicence Forced swim test nationallicence Wieland Scott Department of Psychiatry, University of Pennsylvania, 207 Piersol Building, 3400 Spruce Street, 19104-4283, Philadelphia, PA, USA aut Lucki Irwin Department of Psychiatry, University of Pennsylvania, 207 Piersol Building, 3400 Spruce Street, 19104-4283, Philadelphia, PA, USA aut Psychopharmacology Springer-Verlag 101/4(1990-08-01), 497-504 0033-3158 101:4<497 1990 101 213 https://doi.org/10.1007/BF02244228 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02244228 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wieland Scott Department of Psychiatry, University of Pennsylvania, 207 Piersol Building, 3400 Spruce Street, 19104-4283, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Lucki Irwin Department of Psychiatry, University of Pennsylvania, 207 Piersol Building, 3400 Spruce Street, 19104-4283, Philadelphia, PA, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 101/4(1990-08-01), 497-504 0033-3158 101:4<497 1990 101 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer