NEUROPEPTIDE-Y ATTENUATES NALOXONE-PRECIPITATED MORPHINE-WITHDRAWAL VIA Y5-LIKE RECEPTORS

The effects of intracerebroventricular injection of neuropeptide Y (NP Y) and various NPY-related peptides were studied on naloxone-precipita ted withdrawal from morphine in rats. The withdrawal reaction was asse ssed using an overall motor score, including jumping, wet dog shakes a nd 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 s core. A less prominent inhibitory effect was revealed on the nonmotor score. At 6 nmol, [Leu31,Pro34]-NPY, NPY 3-36, peptide YY and human pa ncreatic polypeptide all significantly attenuated the motor score, whe reas NPY 13-36 was without effect. This pharmacological profile sugges ts 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 tar get in opioid dependence and withdrawal.