Psychostimulant Drugs and Neuroplasticity 英文参考文献.docVIP

Pharmaceuticals 2011, 4, 976-991; doi:10.3390/ph4070976 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Psychostimulant Drugs and Neuroplasticity Emilio Fernandez-Espejo * and Nieves Rodriguez-Espinosa Departamento de Fisiología Médica, Facultad de Medicina, Universidad de Sevilla, Av. Sanchez Pizjuan 4, 41009 Sevilla, Spain * Author to whom correspondence should be addressed; E-Mail: efespejo@us.es; Tel.: +34-95-455-6584; Fax: +34-95-455-1769. Received: 19 April 2011; in revised form: 15 June 2011 / Accepted: 23 June 2011 / Published: 30 June 2011 Abstract: Drugs of abuse induce plastic changes in the brain that seem to underlie addictive phenomena. These plastic changes can be structural (morphological) or synaptic (biochemical), and most of them take place in the mesolimbic and mesostriatal circuits. Several addiction-related changes in brain circuits (hypofrontality, sensitization, tolerance) as well as the outcome of treatment have been visualized in addicts to psychostimulants using neuroimaging techniques. Repeated exposure to psychostimulants induces morphological changes such as increase in the number of dendritic spines, changes in the morphology of dendritic spines, and altered cellular coupling through new gap junctions. Repeated exposure to psychostimulants also induces various synaptic adaptations, many of them related to sensitization and neuroplastic processes, that include up- or down-regulation of D1, D2 and D3 dopamine receptors, changes in subunits of G proteins, increased adenylyl cyclase activity, cyclic AMP and protein kinase A in the nucleus accumbens, increased tyrosine hydroxylase enzyme activity, increased calmodulin and activated CaMKII in the ventral tegmental area, and increased deltaFosB, c-Fos and AP-1 binding proteins. Most of these changes are transient, suggesting that more lasting plastic br