dopamine Sample Clauses

dopamine. The mesocorticolimbic dopamine system plays a critical role in the behavioural and reinforcing effects of all classes of abused drugs. In the following paragraphs, the focus is on psychostimulants. The evidence presented is based on studies using the self-administration paradigm that, to date, is the most representative animal model for aspects of human drug abuse. Some methodological considerations regarding this model are described in box 1. Psychostimulants such as cocaine and amphetamine increase extracellular do- pamine concentrations in the NAc to a greater extent than in the CP 170, an effect which is most pronounced in the NAc shell subregion 526. It was demonstrated with selective lesions that drug-induced dopamine release in the NAc, but not the dorsal striatum, is critical for the locomotor stimulant effect of cocaine and amphetamine 344,345, which is considered to have predictive value for the reinforcing properties of these drugs 733. During cocaine and amphetamine self-administration, extracellular dopamine levels in the NAc are tonically elevated 171,503 and fluctuate with pha- sic increases just after, and phasic decreases just before, infusions 234,537,734. These observations have led to the hypothesis that animals self-administer the drugs to compensate for the falling concentrations of dopamine. Cocaine and amphetamine are self-administered directly into the NAc 104,440,506,569, primarily in the shell subregion 569, and dopamine-selective lesions in the VTA or NAc attenuate maintenance of psychostimulant self-administration 79,409,502,556,557, whereas their effects on initiation of this behaviour are more controversial 235,409. By contrast, destruction of noradrenergic or serotonergic neurons does not influence psychostimulant self-administration 213,556. Paradoxically, whereas lesions attenu- ate self-administration, dopamine D1 and D2 receptor antagonists administered systemically or directly into the VTA, NAc or amygdala, enhance the rate of psy- chostimulant-maintained self-administration 8,78,299,301,411,439,506,538,750 while reducing the motivation to obtain the drug under a progressive ratio schedule 28,299,439,538. The increase in drug intake is thought to reflect a decrease in the magnitude of the reinforcer, which is in agreement with the reduced motivation to obtain cocaine. box 1: The self-administration model.
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