PKA can modulate reinstatement of drug-seeking behavior in cocaine-withdrawn rats. Injection of Rp-cAMPS into the NAc of cocaine-withdrawn rats increases responding on cocaine-associated levers.110 In addition, intraperitoneal priming doses of the D2 agonists 7-OH-DPAT or quinpirole, which can decrease PKA activity via Gαi/o, increase responding on cocaine-associated levers in cocaine-withdrawn rats. The D1 agonist SKF82958, which activates PKA via Gαs has a minimal effect.123 Therefore, although decreasing PKA activity increases drug seeking in cocaine-withdrawn animals, pharmacological strategies that increase PKA activity are unlikely to be effective in reducing reinstatement of cocaine self-administration.
