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The aim of the study was to examine the effect of manipulating the brain dopamine system, using a D₃ receptor antagonist, on approach responses to food cues in overweight and obese individuals. Twenty-six healthy overweight and obese participants were randomly assigned to receive either a single dose of dopamine D₃ receptor antagonist, GSK598809 (175 mg), or placebo in the first assessment session and vice versa in the second session. Using a stimulus-response compatibility task, approach bias was indexed by response latency to move an image of a manikin towards, versus away from, pictures of food, relative to nonfood stimuli. Data from the first session (which were unaffected by repeated testing) indicated that approach bias scores were significantly reduced in overweight and obese participants who received GSK598809, compared with those who received placebo. Data from the second session were confounded by an effect of treatment order and, consequently, were uninformative for the hypotheses. Between-participant comparison of drug versus placebo conditions indicated that GSK598809 attenuated approach bias to food cues, which is consistent with the reduction in their motivational attractiveness. The findings, albeit preliminary, are in agreement with the view that D₃ receptor antagonists may prove useful as therapeutic agents for reducing appetitive responses to food cues in obesity.

Animal models of nicotine dependence are fundamental experimental tools for the understanding of the neurobiological and molecular processes underlying smoking behaviour. Substance use is controlled by four main processes: positive reinforcing effects, aversive effects, discriminative effects and stimulus-conditioned effects of the drug. In this article, the molecular and neural bases of the positive reinforcing effects of nicotine are summarized, focusing on data obtained in experiments including unambiguous and objective measurements of the reinforcing properties of nicotine. Operant behaviour paradigms, in particular intravenous nicotine self-administration, offer such a possibility within a solid theoretical framework. Nicotine self-administration produces changes in the mesocorticolimbic DA system, a key component of the reward system, as do other addictive drugs. The role of the mesocorticolimbic DA system as the main substrate of the reinforcing properties of nicotine is supported by converging experiments, including the evidence that nicotine self-administration is attenuated in mutant mice lacking the beta2 subunit of neural acetylcholine nicotinic receptor. The long-term adaptive molecular changes in the target neurons of the terminal fields of the mesocorticolimbic DA system, including transcriptional regulation mediated by c-fos family gene products on other genes, suggest that the mesolimbic DA projection to the nucleus accumbens is mainly involved in the stimulus-reward learning process. These data represent an initial set of information only, which may help to develop a more complete and reliable model of the molecular dynamics underlying the reinforcing effects of nicotine.