Neuropeptide Y Attenuates Naloxone-Precipitated Morphine Withdrawal via Y5-like Receptors1
- 1Laboratory of Neuropharmacology, Department of Pharmacology, University of Copenhagen, (D.P.D.W., K.K.); 2Laboratory for Experimental Neuropsychiatry, Department of Psychiatry, University Hospital, Rigshospitalet, Copenhagen (T. M. M.), Denmark.
Abstract
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.
Footnotes
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Send reprint requests to: Dr. David P.D. Woldbye, Laboratory of Neuropharmacology, Department of Pharmacology, University of Copenhagen, 3 Blegdamsvej, DK-2200, Copenhagen N, Denmark
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↵1 This work was supported by the Danish Medical Research Council (12-1343), Ivan Nielsens Foundation, Eli and Egon Larsens Foundation, the Research Grant of Einar Geert-Jørgensen and his wife Ellen Geert-Jørgensen, the Danish Psychiatric Research Foundation and the Gangsted Foundation.
- Abbreviations:
- NPY
- neuropeptide Y
- hPP
- human pancreatic polypeptide
- PYY
- peptide YY
- WDS
- wet dog shakes
- i.c.v.
- intracerebroventricular
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- Received June 10, 1997.
- Accepted October 27, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
