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The Journal of Neuroscience, 2000, 20:RC62:1-5
RAPID COMMUNICATION
Distinct Sites of Opiate Reward and Aversion within the Midbrain
Identified Using a Herpes Simplex Virus Vector Expressing GluR1
William A.
Carlezon Jr1,
Colin N.
Haile1,
Robert
Coopersmith2,
Yasunori
Hayashi3,
Roberto
Malinow3,
Rachael L.
Neve2, and
Eric J.
Nestler1
1 Division of Molecular Psychiatry, Center for Genes
and Behavior, Yale University School of Medicine and Connecticut Mental
Health Center, New Haven, Connecticut 06508, 2 Department
of Genetics, Harvard Medical School, McLean Hospital, Belmont
Massachusetts 02478, and 3 Cold Spring Harbor Laboratory,
Cold Spring Harbor, New York 11724
Repeated administration of morphine increases expression of GluR1
(an AMPA glutamate receptor subunit) in the ventral tegmental area
(VTA) of the midbrain, an important neural substrate for the rewarding
actions of morphine. Microinjections of a herpes simplex virus (HSV)
vector that causes local overexpression of GluR1 (HSV-GluR1) into the
VTA can enhance the ability of morphine to establish conditioned place
preferences, suggesting that altered GluR1 expression in this region is
directly associated with changes in the rewarding efficacy of morphine.
We now report that in rats given HSV-GluR1 directly into the VTA,
morphine is most rewarding when maximal transgene expression is in the
rostral VTA, whereas morphine is aversive when maximal transgene
expression is in the caudal VTA. Dual-labeling immunohistochemistry
shows that this difference cannot be explained by a different fraction
of dopaminergic neurons infected in the rostral versus caudal VTA. No
such anatomical specificity is seen in rats given VTA microinjections
of HSV-LacZ, a vector expressing a control protein ( -galactosidase).
These results suggest that distinct substrates within the VTA itself differentially contribute to the rewarding and aversive properties of opiates.
Key words:
morphine; reward; place conditioning; glutamate; AMPA; viral vector
Copyright © 2000 Society for Neuroscience 0270-6474/00/$05.00/0
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