Abstract

The striatal D 1 dopamine receptor (D 1 R) and A 2a adenosine receptor (A 2a R) signaling pathways play important roles in drug-related behaviors. These receptors activate the G olf protein comprised of a specific combination of α olf β 2 γ 7 subunits. During assembly, the γ 7 subunit sets the cellular level of the G olf protein. In turn, the amount of G olf protein determines the collective output from both D 1 R and A 2a R signaling pathways. This study shows the Gng7 gene encodes multiple γ 7 transcripts differing only in their non-coding regions. In striatum, Transcript 1 is the predominant isoform. Preferentially expressed in the neuropil, Transcript 1 is localized in dendrites where it undergoes post-transcriptional regulation mediated by regulatory elements in its 3′ untranslated region that contribute to translational suppression of the γ 7 protein. Earlier studies on gene-targeted mice demonstrated loss of γ 7 protein disrupts assembly of the G olf protein. In the current study, morphological analysis reveals the loss of the G olf protein is associated with altered dendritic morphology of medium spiny neurons. Finally, behavioral analysis of conditional knockout mice with cell-specific deletion of the γ 7 protein in distinct populations of medium spiny neurons reveals differential roles of the G olf protein in mediating behavioral responses to cocaine. Altogether, these findings provide a better understanding of the regulation of γ 7 protein expression, its impact on G olf function, and point to a new potential target and mechanisms for treating addiction and related disorders.