Drug addiction: the neurobiology of behaviour gone awry

Abstract

Drug addiction manifests as a compulsive drive to take a drug despite serious adverse consequences. This aberrant behaviour has traditionally been viewed as bad "choices" that are made voluntarily by the addict. However, recent studies have shown that repeated drug use leads to long-lasting changes in the brain that undermine voluntary control. This, combined with new knowledge of how environmental, genetic and developmental factors contribute to addiction, should bring about changes in our approach to the prevention and treatment of addiction.

The role of the central ghrelin system in reward from food and chemical drugs

“…Interestingly, there appears to be co-morbidities between eating disorders (specifically binge eating) and drug dependence (eg Anzengruber et al 2006;Bulik 1991) and human imaging studies reveal an underlying disruption in the reward systems in addictive behaviours, including alcohol use disorder and binge eating Volkow and Li 2004). Therefore we suggest that similar mechanisms may play a role in multiple addictions and that central ghrelin signalling at the level of the cholinergic-dopaminergic reward link play an important role.…”

The GABAB Receptor-Positive Modulator GS39783 and the GABAB Receptor Agonist Baclofen Attenuate the Reward-Facilitating Effects of Cocaine: Intracranial Self-Stimulation Studies in the Rat

“…Currently, there is an increasing interest in the development of nondopaminergic pharmacotherapies for various drug addictions (Cryan et al, 2003b;Gorelick et al, 2004;Volkow and Li, 2004;Sofuoglu and Kosten, 2005). Blockade of the acute rewarding effects of abused drugs such as cocaine can occur via three principles (i) as a substitute for cocaine, thus leading to similar neurochemical effects (Gorelick et al, 2004;Heidbreder and Hagan, 2005;Sofuoglu and Kosten, 2005); (ii) as a cocaine antagonist by blocking the binding of cocaine to the dopamine transporter (Desai et al, 2005); or (iii) as a ligand acting at a site independent of cocaine effects (Gorelick et al, 2004) such as with GABA B receptor modulators.…”

“…Blockade of the acute rewarding effects of abused drugs such as cocaine can occur via three principles (i) as a substitute for cocaine, thus leading to similar neurochemical effects (Gorelick et al, 2004;Heidbreder and Hagan, 2005;Sofuoglu and Kosten, 2005); (ii) as a cocaine antagonist by blocking the binding of cocaine to the dopamine transporter (Desai et al, 2005); or (iii) as a ligand acting at a site independent of cocaine effects (Gorelick et al, 2004) such as with GABA B receptor modulators. Further, it is clear that there are many more facets to the addiction process that need to be addressed in order to develop successful pharmacotherapeutic strategies; tackling drug-induced withdrawal; and craving being of paramount importance Therefore, interventions should not be limited to inhibiting the rewarding effects of a drug, but should also include strategies to enhance the saliency value of natural reinforcers, strengthen inhibitory control, decrease conditioned responses, and improve withdrawal-induced deficits in mood and anxiety (Volkow and Li, 2004). The fact that GABA B receptor-positive modulators reduce anxiety in preclinical paradigms suggests that they may assist in the treatment of addiction beyond simply reducing the primary rewarding effects of the reinforcer.…”

The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice

“…Interestingly, human imaging studies reveal an underlying disruption in the reward systems in addictive behaviours including binge eating and alcohol dependence (Volkow et al, 2003;Volkow and Li, 2004;Reuter et al, 2005). Moreover, a co-morbidity of addictive behaviours is well documented, where alcohol-use disorder is frequent in the anorexia nervosa binge eating subtype and in individuals with bulimia nervosa (Henzel, 1984;Bulik et al, 1992).…”