Sensitization to Morphine Induced by Viral-Mediated Gene Transfer

Author:

Carlezon William A.123,Boundy Virginia A.123,Haile Colin N.123,Lane Sarah B.123,Kalb Robert G.123,Neve Rachael L.123,Nestler Eric J.123

Affiliation:

1. W. A. Carlezon Jr., V. A. Boundy, C. N. Haile, S. B. Lane, E. J. Nestler, Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.

2. R. G. Kalb, Departments of Neurology and Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

3. R. L. Neve, Department of Genetics, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA.

Abstract

Repeated administration of morphine sensitizes animals to the stimulant and rewarding properties of the drug. It also selectively increases expression of GluR1 (an AMPA glutamate receptor subunit) in the ventral tegmental area, a midbrain region implicated in morphine action. By viral-mediated gene transfer, a causal relation is shown between these behavioral and biochemical adaptations: Morphine's stimulant and rewarding properties are intensified after microinjections of a viral vector expressing GluR1 into the ventral tegmental area. These results confirm the importance of AMPA receptors in morphine action and demonstrate specific locomotor and motivational adaptations resulting from altered expression of a single localized gene product.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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