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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

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Copyright © 2000 Society for Neuroscience  0270-6474/00/$05.00/0

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