Neuropeptide Y attenuates cocaine-primed reinstatement of a self-administration response in rats

Neuropeptide Y (NPY) is a neurotransmitter that acts on the neural substrates that underlie drug use and dependence. We tested the hypothesis that intracerebroventricular (ICV) NPY administration attenuates cocaine-primed reinstatement of self-administration (SA) behavior in rats with a history of cocaine SA followed by extinction training. Male Long-Evans rats were allowed to self-administer cocaine (0.5 mg/kg, IV) for 21 3-h sessions by snout-poking. Each snout-poke into an active (cocaine-paired) hole initiated a cocaine infusion and a cued 25-sec timeout period in which no cocaine infusions were allowed. After 3 wks, snout-poking in the active hole was extinguished by exposure to the cocaine SA procedure, without cocaine infusions, for 21 sessions. After extinction, rats were tested twice for reinstatement of the snout-poking response: once after a cocaine prime (10 mg/kg, IP) and once after a saline prime (1 ml/kg, IP). NPY was administered (0, 0.1, 0.3, or 1.0 nmol, ICV) 30 min before each reinstatement test. Active and inactive snout-poking responses and number of cocaine infusions (or “sham” infusions) were measured. The cocaine prime significantly increased snout-poking in the active hole compared to the response rate during the saline-primed test OR extinction and did not affect the snout-poking response in the inactive hole. ICV NPY (0.3 and 1.0 nmol) significantly reduced snout-poking in the active hole during the cocaine-primed test and did not affect snout-poking during the saline-primed test. These findings support the idea that central administration of NPY decreases the strength of cocaine and cocaine-associated cues to induce drug-seeking behavior.