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Sensitization to morphine induced by viral-mediated gene transfer
W A Carlezon1, V A Boundy, C N Haile
1Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.
Science (New York, N.Y.)
|August 8, 1997
Summary
Repeated morphine use increases drug effects by altering AMPA receptors (GluR1) in the brain. Enhancing GluR1 expression in the ventral tegmental area directly intensifies morphine
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Repeated morphine administration leads to sensitization of its stimulant and rewarding effects.
- This sensitization is associated with increased expression of GluR1, an AMPA glutamate receptor subunit, in the ventral tegmental area (VTA).
Purpose of the Study:
- To establish a causal link between increased GluR1 expression in the VTA and the behavioral adaptations observed after repeated morphine exposure.
- To investigate the role of AMPA receptors in the neurobiological mechanisms underlying morphine sensitization.
Main Methods:
- Utilized viral-mediated gene transfer to selectively increase GluR1 expression in the VTA of experimental animals.
- Administered morphine repeatedly and assessed behavioral responses, including stimulant and rewarding properties.
Main Results:
- Microinjections of a viral vector expressing GluR1 into the VTA intensified the stimulant and rewarding effects of morphine.
- Demonstrated a direct correlation between enhanced GluR1 expression and behavioral sensitization to morphine.
Conclusions:
- Confirmed the critical role of AMPA receptors, specifically GluR1, in mediating the effects of morphine.
- Showed that altered expression of a single, localized gene product (GluR1) can drive specific locomotor and motivational adaptations related to drug use.