Role of Calcium Channels in Drug Dependence

Abstract

Drug addiction is a medical illness that has devastating health, social, political and economic consequences. Indeed, it is one of the most important health problems facing the world today. Addiction has this devastating impact despite extensive political effort and social/behavioral research aimed at reducing addiction. Social and psychological approaches to the treatment of addiction — while beneficial to many — have been only partially successful in alleviating the worldwide burden of substance abuse (Koob and Le Moal, 1997; Nestler and Aghajanian, 1997; O’Brien, 1997). Based on recent scientific advances, attitudes toward addiction and approaches to the treatment and prevention of addiction are rapidly changing. It is now clear that addiction should be conceptualized as a brain disease that occurs in susceptible individuals as a consequence of cellular and molecular changes in nervous system function (Koob et al, 1998). It is well established that certain brain circuits, like those involving mesencephalic dopaminergic neurons, are particularly important for mediating the behavioral and psychological actions of drugs abuse (Koob and Le Moal, 1997; Rodriguez de Fonseca and Navarro, 1998). This has led to the development of more sophisticated molecular hypotheses to explain critical features of addiction such as sensitization, tolerance, withdrawal and dependence (Nestler and Aghajanian, 1997; Koob et al., 1998). Molecular pharmacology research as well as genetic studies in inbred strains of rodents and the achievement of genetically modified animals have allowed to find those molecular targets of major abused drugs (Guppy et al., 1995; Koob et al., 1998; Crabbe et al., 1999; Ledent et al., 1999).