Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H
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作者:
Logrip, Marian L.
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Ernest Gallo Res Ctr, Emeryville, CA 94608 USA
Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USAErnest Gallo Res Ctr, Emeryville, CA 94608 USA
Logrip, Marian L.
[1
,2
]
Janak, Patricia H.
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机构:
Ernest Gallo Res Ctr, Emeryville, CA 94608 USA
Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USAErnest Gallo Res Ctr, Emeryville, CA 94608 USA
Janak, Patricia H.
[1
,2
,3
]
Ron, Dorit
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机构:
Ernest Gallo Res Ctr, Emeryville, CA 94608 USA
Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USAErnest Gallo Res Ctr, Emeryville, CA 94608 USA
Ron, Dorit
[1
,2
,3
]
机构:
[1] Ernest Gallo Res Ctr, Emeryville, CA 94608 USA
[2] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
Alcoholism is a pervasive social problem, and thus understanding factors that regulate alcohol (ethanol) reward is important for designing effective therapies. One putative regulatory system includes the kappa opioid receptor (KOR) and its endogenous ligand, dynorphin. Previously, we demonstrated that acute ethanol increased preprodynorphin expression via brain-derived neurotrophic factor (BDNF) in striatal neurons, and that blockade of the KOR attenuated decreases in ethanol intake observed following increased expression of BDNF. As high doses of KOR agonists can generate an aversive state, we hypothesized that endogenous dynorphin may regulate ethanol intake by interfering with the rewarding properties of ethanol. We found that low, nonaversive doses of the KOR agonist U50,488H blocked the rewarding properties of ethanol during conditioning, thus impairing the acquisition of conditioned place preference. Importantly, we demonstrate that U50,488H also inhibited the conditioned increase in locomotor activation normally observed in the ethanol-paired chamber on test day. Taken together, these data indicate that the KOR/dynorphin system may acutely regulate ethanol intake via inhibition of the rewarding properties of ethanol. (C) 2009 Elsevier Inc. All rights reserved.
机构:Temple Univ, Lewis Katz Sch Med, Ctr Subst Abuse Res CSAR, 3500 North Broad St,MERB 851, Philadelphia, PA 19140 USA
Huang, Peng
Gentile, Taylor A.
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机构:Temple Univ, Lewis Katz Sch Med, Ctr Subst Abuse Res CSAR, 3500 North Broad St,MERB 851, Philadelphia, PA 19140 USA
Gentile, Taylor A.
Muschamp, John W.
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机构:Temple Univ, Lewis Katz Sch Med, Ctr Subst Abuse Res CSAR, 3500 North Broad St,MERB 851, Philadelphia, PA 19140 USA
Muschamp, John W.
Liu-Chen, Lee-Yuan
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Temple Univ, Lewis Katz Sch Med, Ctr Subst Abuse Res CSAR, 3500 North Broad St,MERB 851, Philadelphia, PA 19140 USATemple Univ, Lewis Katz Sch Med, Ctr Subst Abuse Res CSAR, 3500 North Broad St,MERB 851, Philadelphia, PA 19140 USA