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Dr Anne Lingford-Hughes, Psychopharmacology Unit, School of Medical Science, University of Bristol, Bristol BS8 1TD, UK. Tel: 0117 925 3066; fax: 0117 927 7057; e-mail: [email protected]
Drug and alcohol misuse result in immense harm at both individual and societal level. Our understanding of the neuropharmacology of these disorders is increasing through the use of approaches such as neuroimaging and gene targeting and the availability of specific receptor agonists and antagonists. Our aim here is to describe some interesting new findings that are likely to inform advances in treatment.
THE DOPAMINERGIC PATHWAY
Reward
Over the past 20 years there has been immense interest in the mesolimbic dopaminergic system; most drugs of misuse (except benzodiazepines) increase dopamine here. It is widely accepted that increased levels of dopamine in the nucleus accumbens are key in mediating the rewarding effects or positive reinforcement of drugs of misuse (Koob & Le Moal, 2001). Evidence is still accruing to support this. For instance, alcohol and morphine are no longer rewarding in mice lacking the D2 receptor (D2 knockout mice; Maldonado et al, 1997; Risinger et al, 2000). In humans, Volkow et al (1999) showed in a series of neuroimaging studies using cocaine or methylphenidate that increased dopamine levels in the brain were associated with euphoria and pleasure. Interestingly, low levels of dopamine D2 receptors were associated with pleasure after methylphenidate in drug-naïve individuals, whereas high receptor levels were associated with unpleasant feelings. This study gives us an insight into the role of neurobiology in explaining why drug use for some people is pleasurable and likely to be repeated and for others is unpleasant and not repeated.
Anticipation
The role of dopamine in addiction is now recognised as critical in anticipation and withdrawal as well. In an elegant series of experiments, Schultz (2001) found that in primates trained to associate a cue with a pleasurable experience (food), increased dopaminergic activity was seen in response to the cue and not to the food. If the food was not then presented, dopaminergic function dropped. Reduced dopaminergic function is thought to be associated with negative affect (e.g. dysphoria). Thus, an individual with an addiction may see a ‘cue’ (e.g. a public house, mirror or needle) and if their drug of...