This proposal will test the hypothesis that acute and chronic changes in the ability to activate PKA dependent phosphorylation underlie addictive behaviors and involves generating two constructs that will allow expression of CRE recombinase in a cell specific and temporal fashion. This recombinase will be used to turn on activating and inhibitory protein kinase A (PKA) mutations in dopamine D1 or D2 receptor expressing cells in order to investigate the effects of altered kinase activity on drug seeking behavior and relapse. We hypothesize that mutations that activate PKA activity in D1 receptor expressing cells will inhibit self-administration and relapse of drug taking behavior while mutations that inhibit PKA activity in D2 expressing cells will enhance drug seeking behavior and induce relapse. A detailed understanding of the molecular changes that occur in specific brain regions during chronic drug exposure that underlie the subsequent behavioral changes may provide novel therapeutic targets for pharmacological intervention.
