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 Previous Article
Volume 16, Number 9,
Issue of May 1, 1996
pp. 3112-3122
Copyright ©1996 Society for Neuroscience
Rewarding Actions of Phencyclidine and Related Drugs in Nucleus
Accumbens Shell and Frontal Cortex
Received Sept. 26, 1995; revised Jan. 23, 1996; accepted Jan. 30, 1996.
William A. Carlezon, Jr. and
Roy A. Wise
Center for Studies in Behavioral Neurobiology, Department of
Psychology, Concordia University, Montréal, Québec, Canada
H3G 1M8
Rats learned to lever-press when such behavior was reinforced by
microinjections of phencyclidine (PCP) directly into the
ventromedial (shell) region of nucleus accumbens, indicating that
the drug has direct rewarding actions in that region. Separate
groups of rats learned to lever-press when reinforced with
microinjections of dizocilpine (MK-801) or
3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP), drugs known to
block NMDA receptor function but not dopamine uptake, into the same
region. Each drug was ineffective or markedly less effective when
injected at a slightly more dorsal and lateral site in the core of
nucleus accumbens. Self-administration of PCP, MK-801, or CPP directly
into nucleus accumbens was not altered by co-infusion of a dose of the
dopamine antagonist sulpiride that effectively blocked intracranial
self-administration of the dopamine uptake inhibitor nomifensine,
suggesting that the rewarding actions of the NMDA receptor antagonists
are not dopamine-dependent. Rats also developed lever-pressing habits
when PCP, MK-801, and CPP were each microinjected directly into frontal
cortex, a region previously associated with the rewarding actions of
cocaine but not nomifensine. Thus nucleus accumbens and frontal cortex
are each potential substrates for the rewarding properties of PCP and
related drugs, and the ability of these drugs to disrupt NMDA receptor
function seems sufficient to account for their rewarding actions. When
considered with independent evidence, the present results suggest a
model of drug reward within which the critical event is inhibition of
medium spiny neurons in nucleus accumbens.
Key words:
phencyclidine;
MK-801;
CPP;
NMDA antagonists;
self-administration;
nucleus accumbens (core, shell);
frontal cortex;
dopamine;
reward
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|
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|
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|
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|
|
|
|
|
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[Full Text]
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|
|
|
|
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|
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|
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278(5335):
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|
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17(14):
5271 - 5280.
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[Full Text]
[PDF]
|
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|
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[Full Text]
[PDF]
|
|
|
|
|
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J. L. Cornish and P. W. Kalivas
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[PDF]
|
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