Rewarding and psychomotor stimulant effects of endomorphin-1: anteroposterior differences within the ventral tegmental area and lack of effect in nucleus accumbens
by
Zangen A, Ikemoto S, Zadina JE, Wise RA.
National Institute on Drug Abuse,
National Institutes of Health, Baltimore, Maryland 21224, USA.
azangen@intra.nida.nih.gov
J Neurosci 2002 Aug 15;22(16):7225-33

ABSTRACT

Endomorphin-1 (EM-1) is a recently isolated endogenous peptide having potent analgesic activity and high affinity and selectivity for the mu-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.

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