Prefrontal dysfunction in drug addiction: Cause or consequence?

Abstract

With at least 15,3 million people suffering from illicit drug use disorders and many more alcohol and tobacco abusers, addiction is a worldwide problem that puts a great burden on society. Traditionally, research has focused on the reinforcing effects of drugs of abuse and the underlying neuronal mechanisms. The mesolimbic dopaminergic pathway is now generally accepted as the main target for drugs of abuse and their motivational value. Recently, however, the involvement of other brain areas in developing the addicted state has gained interest, especially the prefrontal cortex. This region is essential in inhibitory control processes which have been demonstrated to be dysfunctional in people suffering from addiction. The present report focuses on the dissimilarities between prefrontal cortex functioning of the addicted brain and healthy controls. Furthermore, this study discusses whether the abnormalities in prefrontal functioning exhibited by substance abusers are preexisting vulnerability traits which lead to addiction or, alternatively, are induced by repeated exposure to drugs of abuse. Accumulating evidence, particularly from animal studies, supports the latter hypothesis by demonstrating drug-induced structural alterations in the prefrontal cortex and drug-induced abnormal behavior associated with prefrontal regions. Nevertheless, some human studies have revealed individual differences which might predict the susceptibility for developing drug addiction. It is postulated that while underdeveloped prefrontal functioning may reflect a predisposition for drug taking and addiction, the drug-induced alterations are likely to facilitate the transitions from drug use to addiction.