Sensitization to morphine induced by viral-mediated gene transfer.
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.
Carlezon
W A
WA
Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.
Boundy
V A
VA
Haile
C N
CN
Lane
S B
SB
Kalb
R G
RG
Neve
R L
RL
Nestler
E J
EJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003214:Conditioning, Classical; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics* / Q000502:physiology*; D012201:Reward; D018139:Simplexvirus / Q000235:genetics; D019076:Transgenes; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
D002118:Calcium; D009020:Morphine; D018091:Receptors, AMPA; D014446:Tyrosine 3-Monooxygenase