Carlezon, W. A., Haile, C. N., Coopersmith, R., Hayashi, Y., Malinow, R., Neve, R. L., Nestler, E. J. (March 2000) Distinct sites of opiate reward and aversion within the midbrain identified using a herpes simplex virus vector expressing GluR1. Journal of Neuroscience, 20 (5). ISSN 0270-6474
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Abstract
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 (beta-galactosidase). These results suggest that distinct substrates within the VTA itself differentially contribute to the rewarding and aversive properties of opiates.
Item Type: | Paper |
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Uncontrolled Keywords: | morphine reward place conditioning glutamate AMPA viral vector VENTRAL TEGMENTAL AREA NUCLEUS-ACCUMBENS DOPAMINE NEURONS SELF-STIMULATION ADJACENT REGIONS MORPHINE RAT GLUTAMATE ACTIVATION BEHAVIOR |
Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > AMPA receptor organism description > animal behavior bioinformatics > genomics and proteomics > small molecules > Glutamate |
CSHL Authors: | |
Communities: | CSHL labs > Malinow lab |
Depositing User: | Matt Covey |
Date: | March 2000 |
Date Deposited: | 31 Jan 2014 15:37 |
Last Modified: | 31 Jan 2014 15:37 |
Related URLs: | |
URI: | https://repository.cshl.edu/id/eprint/29376 |
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