Neuropeptide Y: intraaccumbens injections produce a place preference that is blocked by cis-flupenthixol

Abstract

Neuropeptide Y (NPY) has been localized in the nucleus accumbens (NAcc), where it may influence dopamine (DA) neurotransmission. Extensive data implicate NAcc DA in reward-related learning, raising the possibility that NPY microinjected into the NAcc may induce rewarding effects mediated by DA. This hypothesis was tested using the conditioned place preference (CPP) paradigm. Each experiment consisted of three distinct phase: preconditioning (three 15-min exposures to an apparatus with two compartments connected by a tunnel); conditioning (four 30-min pairing of one compartment with drug and four similar pairings of the other compartment with vehicle); and test (three 15-min exposures to the apparatus). A significant increase in the time spent in the drug-paired compartment from preconditioning to test was taken as evidence of a CPP. Two experiments showed that systemic (2.0 mg/kg, IP) or intraaccumbens amphetamine (10.0 micrograms in 0.5 microliters on each side) produced a CPP. The third experiment showed that intraaccumbens NPY (0.1 micrograms in 0.5 microliter on each side) produced a CPP. This CPP was blocked by pretreatment with a dose of the DA receptor blocker cis-flupenthixol (20.0 micrograms in 0.5 microliter on each side in the NAcc) that, alone, produced no CPP effect. These results strongly suggest that NPY applied to the NAcc is rewarding. In addition, these rewarding properties of NPY may be mediated by DA neurotransmission.