A conditioning model of alcohol tolerance.

Tolerance to several effects of ethanol can be learned in a classical conditioning paradigm. In the conditioning model of tolerance, a response compensatory in nature to the effect of ethanol develops in association with the cues that signal the presence of ethanol. Tolerance produced by this procedure (environment-dependent tolerance) differs in several respects from tolerance produced in a paradigm in which learning would not be expected to play a significant role (environment-independent tolerance). Depletion of norepinephrine in the brain blocks the development of both types of tolerance, whereas depletion of serotonin enhances the rate of development of environment-dependent tolerance, but inhibits the development of environment-independent tolerance. Cued alterations in the volume of distribution for ethanol are an important factor in the tolerance displayed in the classical conditioning paradigm. It has been suggested that the conditioned compensatory response comprises the physiological response underlying "craving" for ethanol. This implies that an extinction procedure would be an effective treatment for the prevention of relapse.