Neuropharmacology of addiction and how it informs treatment

Department of Experimental Medicine, Imperial College, Burlington Danes Building, Hammersmith Hospital Site, 160 Du Cane Road, London, UK.
British Medical Bulletin (Impact Factor: 3.66). 11/2010; 96(1):93-110. DOI: 10.1093/bmb/ldq032
Source: PubMed


Our knowledge about the neuropharmacology of addiction is increasing and is leading to more informed development of pharmacotherapy. Although the dopaminergic mesolimbic system plays a central role in 'liking', reward and motivation, medications directly targeting it have not proved a very fruitful approach to treating addictions. A review of the literature was performed to find articles relating current and developing pharmacological treatments in the clinic and their underlying neuropharmacology. We focussed on the most common addictions for which pharmacology plays an important role. By characterizing what neurotransmitters modulate this dopaminergic pathway, new medications are now in the clinic and being successfully applied to treat a variety of addictions. In addition to modulating this reward pathway, alternative approaches in the future will target learning and memory, improving impulse control and decision-making.

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    • "Dopamine is related to incentive motivational aspects of rewards which are in turn associated with strong positive affect such as excitement, enthusiasm, and self-confidence (Depue and Collins, 1999). Many drugs of abuse, either directly or indirectly, induce acute release of dopamine from mesolimbic dopamine neurons into the nucleus accumbens in rodents (Di Chiara et al., 2004), while stimulants but not heroin, have been demonstrated to increase dopamine release into the ventral striatum in humans (Lingford-Hughes et al., 2010) with mixed findings with respect to alcohol and dopamine release in humans (Boileau et al., 2003; Yoder et al., 2009). Pleasurable feelings of intoxication correlate with ventral striatal dopamine release for stimulants (Volkow et al., 1999) and alcohol (Boileau et al., 2003) and thus dopamine may be important for the rewarding effects of drugs of abuse (Volkow et al., 2011). "
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    ABSTRACT: Substance dependence is complex and multifactorial, with many distinct pathways involved in both the development and subsequent maintenance of addictive behaviors. Various cognitive mechanisms have been implicated, including impulsivity, compulsivity, and impaired decision-making. These mechanisms are modulated by emotional processes, resulting in increased likelihood of initial drug use, sustained substance dependence, and increased relapse during periods of abstinence. Emotional traits, such as sensation-seeking, are risk factors for substance use, and chronic drug use can result in further emotional dysregulation via effects on reward, motivation, and stress systems. We will explore theories of hyper and hypo sensitivity of the brain reward systems that may underpin motivational abnormalities and anhedonia. Disturbances in these systems contribute to the biasing of emotional processing toward cues related to drug use at the expense of natural rewards, which serves to maintain addictive behavior, via enhanced drug craving. We will additionally focus on the sensitization of the brain stress systems that result in negative affect states that continue into protracted abstinence that is may lead to compulsive drug-taking. We will explore how these emotional dysregulations impact upon decision-making controlled by goal-directed and habitual action selections systems, and, in combination with a failure of prefrontal inhibitory control, mediate maladaptive decision-making observed in substance dependent individuals such that they continue drug use in spite of negative consequences. An understanding of the emotional impacts on cognition in substance dependent individuals may guide the development of more effective therapeutic interventions.
    Frontiers in Integrative Neuroscience 11/2012; 6:101. DOI:10.3389/fnint.2012.00101
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    • "Both drugs reduce relapse risk but through different mechanisms. Acamprosate increases abstinence rates probably by attenuating conditioned responses to alcohol cues, and also reduces the amount drunk in a lapse (Chick et al., 2003; Lingford-Hughes et al., 2010). In contrast, naltrexone , as well as slightly increasing absolute abstinence rates, seems to stop a lapse to alcohol use leading to a relapse. "

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