Journal
NEUROPHARMACOLOGY
Volume 47, Issue -, Pages 242-255Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2004.07.005
Keywords
cocaine; heroin; nucleus accumbens; ventral tegmental area; dopamine receptors; alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors
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Funding
- NIDA NIH HHS [DA 0013796, DA 08227, DA 10460] Funding Source: Medline
- NATIONAL INSTITUTE ON DRUG ABUSE [R29DA010460, R01DA010460, P01DA008227] Funding Source: NIH RePORTER
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Previous studies have identified several neuroadaptations to chronic drug use, but relatively few have been functionally linked to addiction-related changes in drug-taking and -seeking behaviors. This article summarizes our past and present studies on the contribution of drug-induced neuroadaptations in the mesolimbic dopamine system to addiction-related changes in drug self-administration and the propensity for relapse in drug withdrawal. Our studies suggest that drug-induced up-regulation in cyclic AMP (cAMP)-protein kinase A (PKA) signaling in the nucleus accumbens (NAc) contributes to escalating drug intake and a propensity for relapse by differentially altering the sensitivity of D-1 and D-2 dopamine receptors that regulate drug-taking and -seeking behaviors. In addition, our studies suggest that drug-induced neuroplasticity at excitatory synapses in both the ventral tegmental area (VTA) and the NAc also facilitates drug-seeking behavior and the propensity for relapse. Finally, the role of both transient and enduring neuroadaptations in regulating drug-seeking behavior is discussed in view of different learning and memory-based interactions. (C) 2004 Elsevier Ltd. All rights reserved.
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