Manipulation of PKA activity can increase or decrease the self-administration of addictive drugs in rodent models. The direction of the effect varies with the type of addictive drug. Decreasing PKA activity decreases psychostimulant self-administration in rodents. In rats trained to self-administer cocaine, intra-accumbal injections of the PKA inhibitor Rp-cAMPS decrease self-administration, whereas injections of the PKA activator Sp-cAMPS increase self-administration.110 No change in self-administration is seen when Rp-cAMPS or Sp-cAMPS are injected into the caudate-putamen, indicating that the effects of PKA on self-administration are selective for the NAc.110 In progressive ratio paradigms that assess the extent of work that an animal is willing to perform for access to drug, intra-accumbal injections of Rp-cAMPS decrease the breaking point at which rats no longer lever press for cocaine, while Sp-cAMPS increases the breaking point.111 This effect persists for at least 4 days after injection of the PKA modulator.111 These data suggest that PKA in the rat NAc regulates motivation to self-administer cocaine.
