Effects of SUN 8399, a potent and selective 5-HT1A agonist, on conflict behavior and ambulatory activity in mice: comparison with those of buspirone, tandospirone and diazepam.
Behavioral effects of p.o. administration of SUN 8399, a selective 5-HT1A agonist, on the operant behavior under a MULT VI 1.5 min/FR 5-punishment schedule of food reinforcement and on the ambulatory activity were evaluated in mice, and the characteristics were compared with those of other 5-HT1A agonists, buspirone and tandospirone, and the benzodiazepine diazepam. Diazepam (3 and 10 mg/kg) significantly increased the punished response without eliciting any significant change in the non-punished response; i.e., showing anticonflict action. SUN 8399 (3-30 mg/kg) and buspirone (1-10 mg/kg) did not significantly change either the punished or non-punished responses. Tandospirone significantly increased the non-punished response at 10 mg/kg, but significantly decreased both the punished and non-punished responses at 30 mg/kg. The single administration of SUN 8399 (10 mg/kg), buspirone (3 and 30 mg/kg) and tandospirone (10 and 30 mg/kg) significantly increased the ambulatory activity, while diazepam tended to decrease it. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was reduced by buspirone (10 and 30 mg/kg) and tandospirone (10 and 30 mg/kg), but enhanced by diazepam (3 and 10 mg/kg). Buspirone (30 mg/kg), tandospirone (10 and 30 mg/kg) and diazepam (3 and 10 mg/kg) significantly reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.). SUN 8399 (3-100 mg/kg) did not modify the effects of either methamphetamine or scopolamine. The present results suggest that 5-HT1A agonists scarcely show anticonflict action on the Geller-type conflict behavior in mice. However, SUN 8399 possesses different behavioral characteristics from those of the other two 5-HT1A agonists in terms of interactions with methamphetamine and scopolamine.
Kuribara
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Department of Neurobiology and Behavior, Gunma University School of Medicine, Maebashi, Japan.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology*; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D054833:Isoindoles; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010077:Oxazepines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D054833:Isoindoles; D010077:Oxazepines; D010879:Piperazines; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; C088257:SUN 8399; C055267:tandospirone; D003975:Diazepam; D002065:Buspirone