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The Journal of Neuroscience, August 15, 2002, 22(16):7225-7233

Rewarding and Psychomotor Stimulant Effects of Endomorphin-1: Anteroposterior Differences within the Ventral Tegmental Area and Lack of Effect in Nucleus Accumbens

Abraham Zangen¹, Satoshi Ikemoto¹, James E. Zadina², and Roy A. Wise¹

¹ National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, and ² Veterans Affairs Medical Center and Department of Medicine and Neuroscience Program, Tulane University School of Medicine, New Orleans, Louisiana 70112

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.

Key words: endomorphin-1; reward; locomotion; ventral tegmental area; nucleus accumbens; intracranial self administration

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22167225-09$05.00/0

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