Comparative Aspects of Tolerance to, and Dependence on, Alcohol, Barbiturates and Opiates

Abstract

Despite the known differences in mechanism of action of opiates and of the general depressants at molecular level, the withdrawal reactions after prolonged treatment with morphine, alcohol and barbiturates have many features in common. The main differences relate to the more prominent autonomic overactivity in opiate withdrawal, and the more prominent central overactivity (seizures, hallucinations, delirium) in alcohol and barbiturate withdrawal. Most of the neurochemical and neurophysiological phenomena so far examined are common to all three withdrawal reactions and are probably secondary to neuronal hyperactivity, rather than basic mechanisms of physical dependence.The time course of development of tolerance is similar with all three drugs, as is the influence of dose, intensity of exposure, and behavioral demands on the organism during the period of drug action. Daily treatment with morphine in doses ranging from 7.5 to 45 mg/kg resulted in a tolerance curve with two apparently exponential components, an early steeper one and a later, less steep one. The slopes of both components increased with the dose. The suggestion of two components is also supported by differing patterns of within-session tolerance in rats exposed to ethanol before vs. after test sessions.Administration of p-CPA significantly reduced the net rate of development of tolerance to ethanol and to pentobarbital, just as had earlier been shown for morphine. A hypothesis is offered to explain how drugs with very different molecular mechanisms of action can produce adaptive changes with many important features in common.KeywordsPhysical DependenceMorphine ToleranceAlcohol Withdrawal SyndromeOpiate WithdrawalTolerance DevelopmentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.