Acquisition of conditioned reward blocked by intra-accumbens infusion of PD-140548, a CCKA receptor antagonist.

Cholecystokinin (CCK) is an endogenous peptide that is colocalized with dopamine (DA) in some mesolimbic neurons projecting to the nucleus accumbens (NAC). DA has been implicated in the acquisition of conditioned rewarding properties by neutral stimuli [conditioned stimuli (CS)] associated with a primary reward (such as food). A variety of experimental evidence suggests that exogenously applied CCK, acting at the CCKA receptor, potentiates the function of DA in the NAC. Thus, the present experiment examined the role of endogenous CCKA mechanisms in the NAC in the development of conditioned reward. The CCKA receptor-selective antagonist PD-140548 was microinjected into the NAC during the CS-food pairing phase of a conditioned reward experiment. In the test session, animals that previously received vehicle microinjections into the NAC or PD-140548 microinjections into areas surrounding the NAC pressed a lever that produced the CS more often than did a control lever. The CS had gained conditioned rewarding properties. However, animals that received PD-140548 microinjections into the NAC did not exhibit a preference for the CR lever. Results suggest that blockade of CCKA receptors in the NAC impairs the development of conditioned reward. These findings support a role for endogenous CCKA mechanisms in the NAC in the acquisition of stimulus-reward associations.