Mechanisms of Stimulant Drug Dependence

Objectives: Current theories of severe substance use disorder (chemical dependence) have tended to focus on either the initial phases of the process when the individual experiences WANT or on the later phases when the predominant experience is NEED for the drug. The present review integrates these two phases of the dependence process using information from our own formulation in conjunction with other theories plus selected results from the anti-drug craving literature. Methods: We have recently provided an integrated theory of severe substance use disorder (dependence) that integrates incentive sensitization, receptor down-regulation, psychomotor stimulant, and opponent process theories into a framework. The literature that helped to derive these theories was integrated with recent publications by these and other authors from searches done on PubMed using search criteria as follows: review article, free full text, published since 2000, and drug addiction or drug dependence. Results: Persistence of craving implies and neurobiological research has confirmed that chemical dependence changes brain chemistry in those regions of the brain that are associated with emotion, motivation and decision-making (the limbic system). The key parts of the limbic system that are most altered by the chemical dependence process are the mesolimbic/mesocortical dopamine (DA) system and the nigrostriatal DA system. The anatomical substrate of chemical dependence includes specific portions of the DA projections to the forebrain. Significantly, all major theories of drug dependency associate DA in these anatomical pathways with the different stages and effects of drug usage and chemical dependence. We discuss in this paper the relationship between dopamine neuroanatomy and neurophysiology and the well-known drug dependency continuum stretching from LIKE to WANT to NEED. Conclusions: We suggest that there is a continuum of drug abuse extending from LIKE to WANT to NEED and that the phenomena of these states and the transitions among them are explicable in terms of dopamine receptor and dopamine transporter regulation.