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

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

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
JournalNeuropharmacology
Volume47
Issue numberSUPPL. 1
DOIs
StatePublished - 2004

Fingerprint

Drug-Seeking Behavior
Dopamine
Pharmaceutical Preparations
Nucleus Accumbens
Recurrence
Tegmentum Mesencephali
Adenylate Kinase
Dopamine D1 Receptors
Ventral Tegmental Area
Neuronal Plasticity
Self Administration
Dopamine D2 Receptors
Cyclic AMP-Dependent Protein Kinases
Cyclic AMP
Synapses
Up-Regulation
Learning

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system. / Self, David W.

In: Neuropharmacology, Vol. 47, No. SUPPL. 1, 2004, p. 242-255.

Research output: Contribution to journalArticle

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