Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system

David W. Self

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


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 D1 and D2 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.

Original languageEnglish (US)
Pages (from-to)242-255
Number of pages14
Issue numberSUPPL. 1
StatePublished - 2004


  • Cocaine
  • Dopamine receptors
  • Heroin
  • Nucleus accumbens
  • Ventral tegmental area
  • α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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