Behavioral pharmacology of abecarnil in baboons: Self-injection, drug discrimination and physical dependence

The behavioral effects of abecarnil, a β-carboline which has been suggested to function as a partial and/or selective agonist at the benzodiazepine receptor, were assessed in baboons. In a chronic administration study, 100 mg/kg/day abecarnil for 6-8 weeks produced few signs of sedation: lip droop and intention tremor were observed in two of the four baboons. Flumazenil administration (5 mg/kg, i.m.) on day 8 of chronic abecarnil produced only a mild precipitated benzodiazepine withdrawal syndrome. Vehicle substitution after 6-8 weeks of chronic abecarnil produced transient signs of a mild withdrawal syndrome, including decreased food intake, but did not produce vomiting, twitches/jerks or seizures. In a self-injection study, abecarnil (0.032-1.0 mg/kg/injection) did not maintain rates of self-injection above vehicle control levels; higher rates of self-injection were maintained in the same animals by cocaine (0.32 mg/kg/injection) and triazolam (0.01 mg/kg/injection). The highest i.v. abecarnil dose (1.0 mg/kg/injection) produced sedation and ataxia in two of the three baboons. In a drug discrimination study, generalization from lorazepam training conditions (1.8 mg/kg, p.o.) to abecarnil was an increasing function of dose, and maximal drug lever responding occurred reliably in all baboons 5 h after 10-32 mg/kg, p.o. abecarnil administration. Flumazenil (0.32 mg/kg, i.m.), given 4 h after abecarnil, completely antagonized the abecarnil stimulus in test sessions 1 h later. The present experiments show that the behavioral profile of abecarnil is clearly distinguishable from that of benzodiazepines.