Psychopharmacology
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Comparative Study
Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats.
D1-Like agonists are self-administered by drug-naive animals, whereas D2-like agonists reinstate cocaine-seeking behavior, but the rewarding and reinstating effects of D1- and D2-like agonists in pavlovian-based conditioned place preference are equivocal. ⋯ D1, but not D2/D3, agonists mediate rewarding effects and reinstatement of cocaine place preference, but the reinstating effects differ markedly from self-administration paradigms.
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Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: 'liking', learning, and 'wanting'. Does dopamine mostly mediate the hedonic impact of reward ('liking')? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli ('wanting')? Each hypothesis is evaluated here, and it is suggested that the incentive salience or 'wanting' hypothesis of dopamine function may be consistent with more evidence than either learning or 'liking'. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic 'liking' for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal 'wanting', and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive 'wanting' in addiction, but also provides opportunities for experiments to disentangle 'wanting', 'liking', and learning hypotheses. Results from studies that exploited those opportunities are described here. ⋯ In short, dopamine's contribution appears to be chiefly to cause 'wanting' for hedonic rewards, more than 'liking' or learning for those rewards.
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Disruption of CB(1) receptor signaling through the use of CB(1) (-/-) mice or the CB(1) receptor antagonist rimonabant (SR141716) has been demonstrated to impair extinction of learned responses in conditioned fear and Morris water maze tasks. In contrast, CB(1) (-/-) mice exhibited normal extinction rates in an appetitively motivated operant conditioning task. ⋯ These results support the hypothesis that the CB(1) receptor plays a vital role in the extinction of aversive memories but is not essential for extinction of learned responses in appetitively motivated tasks.
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Multicenter Study
Profile of executive deficits in cocaine and heroin polysubstance users: common and differential effects on separate executive components.
Structure of executive function was examined and we contrasted performance of substance dependent individuals (polysubstance users) and control participants on neuropsychological measures assessing the different executive components obtained. Additionally, we contrasted performance of polysubstance users with preference for cocaine vs heroin and controls to explore possible differential effects of the main substance abused on executive impairment. ⋯ Executive functions can be fractionated into four relatively independent components. Chronic drug use is associated with widespread impairment of these four executive components, with cocaine use inducing more severe deficits on inhibition and shifting. These findings show both common and differential effects of two widely used drugs on different executive components.
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Social behaviors are disrupted in several psychiatric disorders. The amygdala is a key brain region involved in social behaviors, and amygdala pathology has been implicated in disease states ranging from social anxiety disorder to autism. ⋯ These models with different gradations of disrupted BLA inhibition could help to study social dysfunction in disorders ranging from social anxiety to autism spectrum disorders.