期刊
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
卷 37, 期 9, 页码 2071-2080出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2013.03.019
关键词
Operant learning; Glutamate; Dopamine; Plasticity; Rat
资金
- NIDA NIH HHS [R01 DA004788] Funding Source: Medline
Dopamine and glutamate serve crucial functions in neural plasticity, learning and memory, and addiction. Contemporary theories contend that these two, widely-distributed neurotransmitter systems play an integrative role in motivational and associative information processing. Combined signaling of these systems, particularly through the dopamine (DA) D1 and glutamate (Glu) N-methyl-n-aspartate receptors (NMDAR), triggers critical intracellular signaling cascades that lead to changes in chromatin structure, gene expression, synaptic plasticity, and ultimately behavior. Addictive drugs also induce long-term neuroadaptations at the molecular and genomic levels causing structural changes that alter basic connectivity. Indeed, evidence that drugs of abuse engage D1- and NMDA-mediated neuronal cascades shared with normal reward learning provides one of the most important insights from contemporary studies on the neurobiology of addiction. Such drug-induced neuroadaptations likely contribute to abnormal information processing and behavior, resulting in the poor decision-making, loss of control, and compulsivity that characterize addiction. Such features are also common to many other neuropsychiatric disorders. Behavior problems, construed as difficulties associated with operant learning and behavior, present compelling challenges and unique opportunities for their treatment that require further study. The present review highlights the integrative work of Ann E. Kelley and colleagues, demonstrating a critical role not only for NMDAR, D1 receptors (D1R), and their associated signaling cascades, but also for other Glu receptors and protein synthesis in operant learning throughout a cortico-striatal-limbic network. Recent work has extended the impact of appetitive learning to epigenetic processes. A better understanding of these processes will likely assist in discovering therapeutics to engage neural plasticity-related processes and promote functional behavioral adaptations. (C) 2013 Elsevier Ltd. All rights reserved.
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