Neuropeptide Y Attenuates Naloxone-Precipitated Morphine Withdrawal via Y5-like Receptors

The effects of intracerebroventricular injection of neuropeptide Y (NPY) and various NPY-related peptides were studied on naloxone-precipitated withdrawal from morphine in rats. The withdrawal reaction was assessed using an overall motor score, including jumping, wet dog shakes and other motor-related signs as well as a nonmotor score. At doses of 3, 6 or 12 nmol, NPY strongly and dose-dependently reduced the motor score. A less prominent inhibitory effect was revealed on the nonmotor score. At 6 nmol, [Leu31,Pro34]-NPY, NPY 3-36, peptide YY and human pancreatic polypeptide all significantly attenuated the motor score, whereas NPY 13-36 was without effect. This pharmacological profile suggests that the antiwithdrawal effect of NPY is mediated via the recently cloned Y5 receptor. Our data are consistent with a potential role for NPY and Y5-like receptors in basic mechanisms and as a therapeutic target in opioid dependence and withdrawal.