Reward Processing by the Opioid System in the Brain

被引:724
作者
Le Merrer, Julie
Becker, Jerome A. J.
Befort, Katia
Kieffer, Brigitte L. [1 ]
机构
[1] IGBMC, Dept Neurobiol & Genet, F-67404 Illkirch Graffenstaden, France
基金
美国国家卫生研究院;
关键词
CONDITIONED PLACE PREFERENCE; VENTRAL TEGMENTAL AREA; RECEPTOR MESSENGER-RNA; NUCLEUS-ACCUMBENS SHELL; PROOPIOMELANOCORTIN GENE-EXPRESSION; MEDIAL PREOPTIC AREA; NICOTINE-INDUCED ANTINOCICEPTION; PROGRESSIVE RATIO SCHEDULE; DORSAL PERIAQUEDUCTAL GRAY; CHRONIC MORPHINE EXPOSURE;
D O I
10.1152/physrev.00005.2009
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Le Merrer J, Becker JAJ, Befort K, Kieffer BL. Reward Processing by the Opioid System in the Brain. Physiol Rev 89: 1379-1412, 2009; doi:10.1152/physrev.00005.2009.-The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin. Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops. Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. This review summarizes our present knowledge on brain sites where the endogenous opioid system controls hedonic responses and is modified in response to drugs of abuse in the rodent brain. We review 1) the latest data on the anatomy of the opioid system, 2) the consequences of local intracerebral pharmacological manipulation of the opioid system on reinforced behaviors, 3) the consequences of gene knockout on reinforced behaviors and drug dependence, and 4) the consequences of chronic exposure to drugs of abuse on expression levels of opioid system genes. Future studies will establish key molecular actors of the system and neural sites where opioid peptides and receptors contribute to the onset of addictive disorders. Combined with data from human and nonhuman primate (not reviewed here), research in this extremely active field has implications both for our understanding of the biology of addiction and for therapeutic interventions to treat the disorder.
引用
收藏
页码:1379 / 1412
页数:34
相关论文
共 431 条
[1]   SEXUAL REINFORCEMENT IS BLOCKED BY INFUSION OF NALOXONE INTO THE MEDIAL PREOPTIC AREA [J].
AGMO, A ;
GOMEZ, M .
BEHAVIORAL NEUROSCIENCE, 1993, 107 (05) :812-818
[2]   CONDITIONED PLACE PREFERENCE PRODUCED BY INFUSION OF MET-ENKEPHALIN INTO THE MEDIAL PREOPTIC AREA [J].
AGMO, A ;
GOMEZ, M .
BRAIN RESEARCH, 1991, 550 (02) :343-346
[3]   Transition from moderate to excessive drug intake: Change in hedonic set point [J].
Ahmed, SH ;
Koob, GF .
SCIENCE, 1998, 282 (5387) :298-300
[4]   Neurobiological evidence for hedonic allostasis associated with escalating cocaine use [J].
Ahmed S.H. ;
Kenny P.J. ;
Koob G.F. ;
Markou A. .
Nature Neuroscience, 2002, 5 (7) :625-626
[5]   Endogenous opioids: overview and current issues [J].
Akil, H ;
Owens, C ;
Gutstein, H ;
Taylor, L ;
Curran, E ;
Watson, S .
DRUG AND ALCOHOL DEPENDENCE, 1998, 51 (1-2) :127-140
[6]   NEW PERSPECTIVES IN BASAL FOREBRAIN ORGANIZATION OF SPECIAL RELEVANCE FOR NEUROPSYCHIATRIC DISORDERS - THE STRIATOPALLIDAL, AMYGDALOID, AND CORTICOPETAL COMPONENTS OF SUBSTANTIA INNOMINATA [J].
ALHEID, GF ;
HEIMER, L .
NEUROSCIENCE, 1988, 27 (01) :1-39
[7]   Morphine-induced changes of gene expression in the brain [J].
Ammon-Treiber, S ;
Höllt, V .
ADDICTION BIOLOGY, 2005, 10 (01) :81-89
[8]  
[Anonymous], 1995, PSYCHOPHARMACOLOGY 4
[9]  
[Anonymous], 2000, Diagnostic and statistical manual of mental disorders, V4th
[10]   Central control of penile erection: Role of the paraventricular nucleus of the hypothalamus [J].
Argiolas, A ;
Melis, MR .
PROGRESS IN NEUROBIOLOGY, 2005, 76 (01) :1-21