n(6)-cyclohexyladenosine and Substance-Related-Disorders

The isolated guinea pig ileum provides a model in which drug dependence can be induced in normal neurons. The characteristics of opiate dependence in the ileum closely resemble those of dependence in whole animals. Convergent dependence on normorphine, clonidine, and adenosine can be separately induced in the ileum in vitro. Use of selective antagonists indicates that both acetylcholine and substance P participate in the withdrawal response associated with all three of these dependencies. The demonstration that adenosine derivatives suppress opiate withdrawal in the guinea pig ileum and in mice raises the possibility that they might act similarly in man. The point at which the dependencies on normorphine, clonidine, and adenosine converge is probably below their separate recognition sites and is possibly at the level of adenylate cyclase regulation.

Topics: Acetylcholine; Adenosine; Animals; Clonidine; Cyclic AMP; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Morphine; Morphine Dependence; Morphine Derivatives; Muscle Contraction; Muscle, Smooth; Myenteric Plexus; Naloxone; Pertussis Vaccine; Scopolamine; Substance P; Substance Withdrawal Syndrome; Substance-Related Disorders; Theophylline; Yohimbine

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.

Topics: Adenosine; Alprazolam; Animals; Drug Tolerance; Male; Mice; Phenylisopropyladenosine; Substance-Related Disorders; Theophylline