Adenosine analogs attenuate tolerance-dependence on alprazolam.

1. Tolerance to and physical dependence on alprazolam were induced in mice by administering two doses of a slow release preparation. 2. Physical dependence was evaluated by the abstinence syndrome induced by flumazenil. Tolerance was studied by measuring the motor incoordination induced by a test dose of alprazolam. 3. The intensity of tolerance was decreased by the administration of L-phenylisopropyl adenosine (L-PIA), cyclopentyl adenosine (CPA), cyclohexyl adenosine (CHA), N-ethylcarboxamide adenosine (NECA), 8-phenyltheophylline (8-PTP) and theophylline (TP). 4. The intensity of the abstinence syndrome induced by flumazenil was attenuated by L-PIA, CPA NECA, TP and 8-PTP. 5. The results suggest that benzodiazepines may exert, at least in part, their effects by involving adenosine in the central nervous system.