Rewarding and psychomotor stimulant effects of endomorphin-1: Anteroposterior differences within the ventral tegmental area and lack of effect in nucleus accumbens

Abraham Zangen, Satoshi Ikemoto, James E. Zadina, Roy A. Wise

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

Endomorphin-1 (EM-1) is a recently isolated endogenous peptide having potent analgesic activity and high affinity and selectivity for the μ-opioid receptor. The present study was designed to investigate the rewarding and psychomotor stimulant effects of EM-1 in specific brain regions. We found that rats would learn without priming or response shaping to lever-press for microinjections of EM-1 into the ventral tegmental area (VTA); responding was most vigorous for high-dose injections into the posterior VTA. Rats did not learn to lever-press for microinjections of EM-1 into the nucleus accumbens (NAS) or regions just dorsal to the VTA. Lever-pressing for EM-1 in the VTA was extinguished when vehicle was substituted for the peptide and was reinstated when EM-1 reinforcement was re-established. Conditioned place preference was established by EM-1 injections into the posterior but not the anterior VTA or the NAS. Injection of EM-1 (0.1-1.0 nmol) into the posterior VTA induced robust increases in locomotor activity, whereas injections into the anterior VTA had very weak locomotor-stimulating effects. When injected into the NAS, EM-1 (0.1-10.0 nmol) did not affect locomotor activity. The present findings implicate the posterior VTA as a highly specific and sensitive site for opioid reward and suggest a role for EM-1-containing projections to the posterior VTA in the rewarding effects of other reinforcers.

Original languageEnglish
Pages (from-to)7225-7233
Number of pages9
JournalJournal of Neuroscience
Volume22
Issue number16
DOIs
StatePublished - 15 Aug 2002
Externally publishedYes

Keywords

  • Endomorphin-1
  • Intracranial self administration
  • Locomotion
  • Nucleus accumbens
  • Reward
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience (all)

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