Role of dopamine D2 receptors in human reinforcement learning.

Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.

Opioidergic and dopaminergic manipulation of gambling tendencies: a preliminary study in male recreational gamblers.

Gambling is characterized by cognitive distortions in the processing of chance and skill that are exacerbated in pathological gambling. Opioid and dopamine dysregulation is implicated in pathological gambling, but it is unclear whether these neurotransmitters modulate gambling distortions. The objective of the current study was to assess the effects of the opioid receptor antagonist naltrexone and the dopamine D2 receptor antagonist haloperidol on gambling behavior. Male recreational gamblers (n = 62) were assigned to receive single oral doses of naltrexone 50 mg, haloperidol 2 mg or placebo, in a parallel-groups design. At 2.5 h post-dosing, participants completed a slot machine task to elicit monetary wins, "near-misses," and a manipulation of personal choice, and a roulette game to elicit two biases in sequential processing, the gambler's fallacy and the hot hand belief. Psychophysiological responses (electrodermal activity and heart rate) were taken during the slot machine task, and plasma prolactin increase was assessed. The tasks successfully induced the gambling effects of interest. Some of these effects differed across treatment groups, although the direction of effect was not in line with our predictions. Differences were driven by the naltrexone group, which displayed a greater physiological response to wins, and marginally higher confidence ratings on winning streaks. Prolactin levels increased in the naltrexone group, but did not differ between haloperidol and placebo, implying that naltrexone but not haloperidol may have been functionally active at these doses. Our results support opioid modulation of cognition during gambling-like tasks, but did not support the more specific hypothesis that naltrexone may act to ameliorate cognitive distortions.

Evaluating care pathways for community psychiatry in England: a qualitative study.

OBJECTIVES: In view of forthcoming 'payment by results' (PbR) for mental health, increasing number of National Health Service (NHS) Trusts are reorganizing their community services for working age adults to create care pathways. However, research base for the care pathways model in mental health is limited. Our NHS Foundation Trust was one of the first to introduce care pathways for community psychiatry in the UK. We have carried out a qualitative study to evaluate how this model works out in practice, including its impact on quality of patient care, mental health professionals and primary care. METHODS: We interviewed doctors, multidisciplinary staff and Trusts managers (19 in total). Transcripts of recorded interviews were coded and analysed thematically using a grounded theory approach. RESULTS: Overall, despite teething problems, working in pathways was generally seen as a positive change. It led to more focused interventions being offered, and practitioners being held to account over clear standards of care. It is more cost-effective and allows for active case management and clear clinical leadership. It is recovery focused and encourages social inclusion. The arbitrary time frame, strict criteria and thresholds for different teams can create issues. Improved communication, flexible and patient-centred approach, staff supervision, and increasing support to primary care were felt to be central to this model working efficiently and effectively. CONCLUSIONS: Introduction of care pathways is an important step towards effective implementation of PbR for mental health. Our study would inform future research into care pathways, facilitate organizational learning and help to improve effectiveness of services.