Regulation of phospholipase Cγ in the mesolimbic dopamine system by chronic morphine administration

Neurotrophic signaling pathways have been implicated in the maintenance of the mesolimbic dopamine system, as well as in changes in this system induced by chronic morphine exposure. We found that many of these signaling pathway proteins are expressed at appreciable levels within the ventral tegmental area (VTA) and related regions, although with substantial regional variation. Moreover, phospholipase C gamma 1 (PLC gamma 1) was significantly and specifically up-regulated within the VTA by 30% following chronic exposure to morphine. PLC gamma 1 mRNA expression is enriched in dopaminergic neurons within the VTA; however, the up-regulation of PLC gamma 1 in this region was not seen at the mRNA level, In contrast to PLC gamma 1, insulin receptor substrate (IRS)-2, a protein involved in phosphatidylinositol 3-kinase signaling, and another putative IRS-like protein were significantly down-regulated within the VTA by 49 and 45%, respectively. Levels of several proteins within the Ras-ERK pathway were not altered. Regulation of neurotrophic factor signaling proteins may play a role in morphine-induced plasticity within the mesolimbic dopamine system.