Drugs of Abuse and Dopamine Cell Activity

Abstract

Drugs of abuse can be divided, on the basis of their electrophysiological effects, into two classes: psychostimulants that decrease dopaminergic activity, and others, the acute administration of which increases dopamine firing rate and pattern. Chronic administration of drugs may mimic better neuronal alterations relevant for understanding mechanisms of drug dependence. The mesolimbic dopamine system is a major target of drugs of abuse, not only after acute administration, but also after a chronic challenge. While the chronic intake of drugs of abuse represents an essential step in the development of drug addiction, the withdrawal syndrome is generally the painful end. The withdrawal syndrome is, thus, an extremely important phase in the process of drug dependence because it combines the positive and negative reinforcing properties of drugs of abuse. This chapter summarizes a series of experiments aimed at investigating the physiological status of mesolimbic dopaminergic neurons during and after withdrawal from two of the most abused drugs: ethanol and morphine. The studies lead us to the conclusion that the apparent depolarization block requires an essential ingredient such as the use of chloral hydrate and thus, is extremely unlikely to be the effect of ethanol withdrawal. Similarly, dopamine neurons recorded from rats made dependent on morphine while experiencing a measurable withdrawal syndrome showed electrophysiological features reminiscent of those observed in ethanolwithdrawn rats. The striking similarity of results obtained with two different chemicals, such as ethanol and morphine, reinforces the view that the mesolimbic dopamine system is profoundly affected by chronic administration and withdrawal of addicting drugs and consequently may be viewed as the target for potential new therapies aimed at ameliorating the psychological discomfort produced by drug withdrawal.