Effect of experimenter-delivered and self-administered cocaine on extracellular β-endorphin levels in the nucleus accumbens

I. Roth-Deri, A. Zangen, M. Aleli, R. G. Goelman, G. Pelled, R. Nakash, I. Gispan-Herman, T. Green, Y. Shaham, Gal Yadid

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

β-endorphin is an endogenous opioid peptide that has been hypothesized to be involved in the behavioral effects of drugs of abuse including psychostimulants. Using microdialysis, we studied the effect of cocaine on extracellular levels of β-endorphin in the nucleus accumbens, a brain region involved in the reinforcing effects of psychostimulant drugs. Experimenter-delivered cocaine (2 mg/kg, i.v.) increased extracellular β-endorphin immunoreactive levels in the nucleus accumbens, an effect attenuated by 6-hydroxy-dopamine lesions or systemic administration of the D1-like receptor antagonist, SCH-23390 (0.25 mg/kg, i.p.). The effect of cocaine on β-endorphin release in the nucleus accumbens was mimicked by a local perfusion of dopamine (5 μM) and was blocked by coadministration of SCH-23390 (10 μM). Self-administered cocaine (1 mg/kg/infusion, i.v.) also increased extracellular β-endorphin levels in the nucleus accumbens. In addition, using functional magnetic resonance imaging, we found that cocaine (1 mg/kg, i.v.) increases regional brain activity in the nucleus accumbens and arcuate nucleus. We demonstrate an increase in β-endorphin release in the nucleus accumbens following experimenter-delivered and self-administered cocaine mediated by the local dopaminergic system. These findings suggest that activation of the β-endorphin neurons within the arcuate nucleus-nucleus accumbens pathway may be important in the neurobiological mechanisms underlying the behavioral effects of cocaine.

Original languageEnglish
Pages (from-to)930-938
Number of pages9
JournalJournal of Neurochemistry
Volume84
Issue number5
DOIs
StatePublished - 1 Mar 2003
Externally publishedYes

Keywords

  • Arcuate nucleus
  • Cocaine
  • Drug self-administration
  • Extinction
  • Microdialysis
  • β-endorphin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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