Sensitization

Jessica Loweth, Paul Vezina

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Exposure to psychostimulant drugs leads to sensitized locomotor responding, nucleus accumbens (NAcc) dopamine (DA) overflow, and drug self-administration upon reexposure to the drug weeks to months later. Calcium-dependent signaling pathways contribute importantly to both the induction and expression of sensitization by these drugs. In particular, calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), a serine/threonine kinase that is highly expressed in forebrain regions such as the NAcc, is known to contribute to the expression of several forms of plasticity including sensitization. Notably, pharmacologically inhibiting CaMKII in the NAcc prevents the expression of sensitized locomotion, NAcc DA overflow, and drug taking. Evidence indicates that CaMKII may act both pre- and postsynaptically in this site to influence the expression of these manifestations of sensitization. Presynaptically in DA neuron terminals, CaMKII regulates sensitized DA overflow. Postsynaptically in medium spiny neurons, it contributes to the upregulation of AMPA receptors, the activation of which is necessary for the expression of sensitization. It is conceivable that interactions between CaMKII-mediated neuroadaptations in both of these sites may underlie the long-lasting maintenance of sensitization by psychostimulant drugs.

Original languageEnglish (US)
Title of host publicationAnimal Models of Drug Addiction
Pages191-205
Number of pages15
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Publication series

NameNeuromethods
Volume53
ISSN (Print)0893-2336
ISSN (Electronic)1940-6045

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Psychiatry and Mental health
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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