Distinct sites of opiate reward and aversion within the midbrain identified using a herpes simplex virus vector expressing GluR1

Repeated administration of morphine increases expression of GluR1 (an AMPA glutamate receptor subunit) in the ventral tegmental area (VTA) of the midb rain, an important neural substrate for the rewarding actions of morphine. Microinjections of a herpes simplex virus (HSV) vector that causes local ov erexpression of GluR1 (HSV-GluR1) into the VTA can enhance the ability of m orphine 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 e xpression is in the rostral VTA, whereas morphine is aversive when maximal transgene expression is in the caudal VTA. Dual-labeling immunohistochemist ry shows that this difference cannot be explained by a different fraction o f dopaminergic neurons infected in the rostral versus caudal VTA. No such a natomical 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 cont ribute to the rewarding and aversive properties of opiates.