Dopamine ups and downs in vulnerability to addictions: a neurodevelopmental model

被引:98
作者
Leyton, Marco [1 ,2 ,3 ,4 ]
Vezina, Paul [5 ,6 ]
机构
[1] McGill Univ, Dept Psychiat, Montreal, PQ, Canada
[2] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada
[3] McGill Univ, Dept Psychol, Montreal, PQ, Canada
[4] Concordia Univ, Ctr Studies Behav Neurobiol, Montreal, PQ H3G 1M8, Canada
[5] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA
[6] Univ Chicago, Comm Neurobiol, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
drug abuse; alcohol abuse; reward; conditioning; sensitization; incentive salience; externalizing; allostasis; COCAINE-SEEKING BEHAVIOR; DRUG-ASSOCIATED STIMULI; NUCLEUS-ACCUMBENS CORE; INDIVIDUAL-DIFFERENCES; STRIATAL DOPAMINE; LOCOMOTOR RESPONSE; FAMILY-HISTORY; RISK-TAKING; ALCOHOL-USE; DEVELOPMENTAL PSYCHOPATHOLOGY;
D O I
10.1016/j.tips.2014.04.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Addictions are commonly presaged by problems in childhood and adolescence. For many individuals this starts with the early expression of impulsive risk-taking, social gregariousness, and oppositional behaviors. Here we propose that these early diverse manifestations reflect a heightened ability of emotionally salient stimuli to activate dopamine pathways that foster behavioral approach. If substance use is initiated, these at-risk youth can also develop heightened responses to drug-paired cues. Through conditioning and drug-induced sensitization, these effects strengthen and accumulate, leading to responses that exceed those elicited by other rewards. At the same time, cues not paired with drug become associated with comparatively lower dopamine release, accentuating further the difference between drug and non-drug rewards. Together, these enhancing and inhibiting processes steer a pre-existing vulnerability toward a disproportionate concern for drugs and drug-related stimuli. Implications for prevention and treatment are discussed.
引用
收藏
页码:268 / 276
页数:9
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