Behavioral pharmacology of tandospirone in baboons: chronic administration and withdrawal, self-injection and drug discrimination.
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.
Sannerud
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CA
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Ator
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NA
Griffiths
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RR
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D054833:Isoindoles; D008140:Lorazepam / Q000494:pharmacology; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D009460:Neurologic Examination / Q000187:drug effects; D010215:Papio; D010424:Pentobarbital / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012646:Self Administration; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D019966:Substance-Related Disorders / Q000523:psychology
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; C055267:tandospirone; D005442:Flumazenil; D010424:Pentobarbital; D003042:Cocaine; D008140:Lorazepam; D002065:Buspirone