What we know and what we need to know about the role of endogenous CCK in psychostimulant sensitization.

The unique distribution of CCK and its receptors and its co-localization with dopamine makes it ideally situated to pay a role in dopamine-mediated reward and psychostimulant sensitization. A number of studies support the hypothesis that CCK acting through the CCK 1 and CCK 2 receptors is an endogenous modulator of dopamine neurotransmission. Behavioral studies with CCK antagonists and CCK 1 receptor mutant rats support a role for endogenous CCK in behavioral sensitization to psychostimulants. CCK microdialysis studies in the nucleus accumbens (NAC) have demonstrated that extracellular CCK is increased in the NAC by psychostimulants, providing neurochemical evidence that CCK could be involved in the behavioral response to psychostimulants. A model for how CCK may be acting in multiple brain regions to foster sensitization is presented and the gaps in our knowledge about the role of CCK in psychostimulant sensitization are described.