Behavioral sensitization or reverse tolerance

One process, behavioral sensitization or reverse tolerance, may increase the chances of uncontrolled ethanol intake and is showing promise in helping to understand how other substances of abuse work. Research has demonstrated that with repeated administration of psychomotor stimulants, such as amphetamine or cocaine, both behavioral and neurochemical responses to a given dose of these drugs are progressively enhanced. This phenomenon contrasts to the well-known observation that repeated drug administration can lead to many diminished responses (i.e., tolerance). A principal endpoint used in the study of behavioral sensitizations locomotion. Glickman and Schiff (4) proposed theory that all positive reinforces should elicit either an approach to localized stimuli or to some generalized form of locomotion. In this way, they linked positive reinforcement to activation of independent homologous paths in the medial forebrain bundle that produces approach behaviors fasted by locomotion. Based on this concept, approach behaviors and operant reinforcement may have common neural mechanisms and they may therefore be homologous. Wise and Bogart (14) extended this theory to the actions of addictive drugs (like ethanol, nicotine, caffeine, barbiturates, benzodiazepines, cannabis, and phencyclidine) which induce psychomotor activation possibly through dopaminergic fibers or their output circuitry. Based on this theory, all major addictive drugs have psychomotor stimulant actions, even if they have sedative actions that override psychomotor arousal. The positive reinforcing effects of these agents are, therefore, related to unconditioned psychomotor stimulant effects, presumably resulting from activation of dopaminergic fibers of the medial forebrain bundle, their inputs, or their outputs.

References

Hunt, Walter A., and William E. Lands. 1992. “A role for behavioral sensitization in uncontrolled ethanol intake.” Alcohol 9 (4): 327–28. doi:10.1016/0741-8329(92)90075-L.