Neuropeptide Y augments cocaine self-administration and cocaine-induced hyperlocomotion in rats

Abstract

Food restriction and deprivation are known to modulate drug-related behaviors. However, the mechanisms through which metabolic manipulations intercede the rewarding effects of drug reward are unknown. Neuropeptide Y (NPY) is thought to be critically involved in the regulation of energy balance. Central administration of NPY induces feeding in sated animals, and importantly, is reported to increase the rewarding properties of food. NPY has also been shown to be involved in drug-related behavior. We have recently demonstrated that NPY injections augmented on-going heroin self-administration and induced a reinstatement of heroin seeking. The present study sought to support and expand our previous finding on NPY's role in addictive drugs-related behaviors by examining the effects of NPY on cocaine-induced locomotor hyperactivity and cocaine self-administration. In Experiment 1, rats received NPY injections (0.0, 2.5, 5.0microg/rat, ICV), followed by cocaine administration (0.0, 1.0, 5.0, and 10.0mg/kg, IP) and their locomotor activity was monitored over 90min. In Experiment 2, rats were trained to self-administer cocaine (0.50mg/kg/infusion) during one 3-h session per day for 12 days. Once trained, NPY (0.0, 4.0, 10.0microg/rat, ICV) was administered 15min prior to the self-administration session. Results revealed that NPY injections augmented cocaine-induced hyperactivity and moderately increased cocaine self-administration. Together with our previous findings, these results suggest that NPY is involved, albeit to a limited extent, in the augmenting effect of food deprivation on drug-related behaviors.