Behavioral pharmacology of tandospirone in baboons: chronic administration and withdrawal, self-injection and drug discrimination.

Abstract

The behavioral pharmacology of tandospirone (SM 3997), a novel anxiolytic/antidepressant pyrimidinylpiperazine compound with selective pharmacological effects at the 5-HT1A binding site, was investigated in baboons. Animals administered 50 mg/kg/day i.g. tandospirone, showed few behavioral changes (lip droop, ataxia), which decreased over 2 weeks. Substitution of vehicle for tandospirone after 7 weeks produced time-limited suppression of food intake, suggesting a mild withdrawal syndrome. Under an i.v. self-injection procedure, tandospirone (1.0-32 mg/kg/injection) did not maintain responding greater than vehicle, although cocaine and triazolam did. Under a drug discrimination procedure, tandospirone (1-3.2 mg/kg p.o.; 0.1-32 mg/kg, i.m.) did not occasion drug-appropriate responding in baboons trained to discriminate lorazepam or pentobarbital and buspirone (1-18 mg/kg, p.o.; 0.1-1.0 mg/kg, i.m.) did not occasion drug-appropriate responding in the pentobarbital-training group. Tandospirone's profile of effects differs from those for barbiturates and benzodiazepines and suggests low abuse liability.