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