期刊
NEUROPHARMACOLOGY
卷 49, 期 4, 页码 525-541出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2005.04.022
关键词
dopamine D-3 receptor; nucleus accumbens shell; conditioned place preference; reward; discrimination; sensitization; cocaine; drug-associated cues
资金
- NATIONAL INSTITUTE ON DRUG ABUSE [ZIFDA000001, ZIADA000001, Z01DA000001, Z01DA000479, Z02DA000001] Funding Source: NIH RePORTER
Abused drugs (alcohol, heroin, cocaine, tetrahydrocannabinol and nicotine) elicit a variety of chronically relapsing disorders by interacting with brain reward systems. All of these drugs increase dopamine levels in the shell of nucleus accumbens, a structure that has been involved in their hedonic and reinforcing properties. Dopamine D-3 receptors (DRD3) are predominantly expressed in the nucleus accumbens, but also in the ventral tegmental area and in the amygdala, brain structures implicated in drug dependence. Moreover, converging pharmacological, human post-mortem and genetic studies have suggested the involvement of the DRD3 in drug dependence. Based on early studies using non-selective DRD3 ligands, the DRD3 was proposed as having a direct role in the rewarding effects of psychostimulants. However, recent studies using highly selective DRD3 ligands and the DRD3-deficient mice have revealed that the DRD3 is not implicated in the direct reinforcing effects of drugs of abuse. In contrast, the DRD3 appears to be implicated in the motivation to self-administer drugs under schedules where the response requirements are high. This is consistent with a behavioral economic analysis, with the effects of DRD3 ligands revealed only in situations with high prices for drug. Drug-self administration and relapse are strongly controlled by environmental stimuli. The DRD3 strongly modulates the influence of these environmental stimuli on drug-seeking behavior. DRD3 blockade disrupts the reactivity to drug-associated stimuli in various paradigms, such as second-order schedules of drug-self administration, conditioned place preference and Pavlovian conditioning procedures. In several paradigms, the involvement of the DRD3 has been confirmed by using DRD3-deficient mice. On the contrary, reactivity to stimuli associated with natural reinforcers, such as food, appears unaffected by modulation of the DRD3. All these findings suggest that DRD3 ligands may represent a useful strategy for decreasing relapse in abstinent drug-abusers. (c) 2005 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据