Supported by Grants AA09981 and AA011605 from the National Institute on Alcohol Abuse and Alcoholism (CWH), by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California at San Francisco, and by the Bowles Center for Alcohol Studies at The University of North Carolina Chapel Hill.
Neuropeptide-Y Y5 Receptors Modulate the Onset and Maintenance of Operant Ethanol Self-Administration
Article first published online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 27, Issue 12, pages 1912–1920, December 2003
How to Cite
Schroeder, J. P., Iller, K. A. and Hodge, C. W. (2003), Neuropeptide-Y Y5 Receptors Modulate the Onset and Maintenance of Operant Ethanol Self-Administration. Alcoholism: Clinical and Experimental Research, 27: 1912–1920. doi: 10.1097/01.ALC.0000098873.80433.BA
- Issue published online: 3 MAY 2006
- Article first published online: 3 MAY 2006
- Received for publication March 18, 2003; accepted September 10, 2003.
- Operant Self-Administration;
- NPY Y5 Receptors
Background: Neuropeptide Y (NPY) is the most abundant and widely distributed peptide in the mammalian central nervous system and increases feeding behavior at NPY Y1 or Y5 receptor subtypes. Recent pharmacological and mutant mouse data indicate that NPY activity at its receptors can influence ethanol self-administration, although the direction and strength of this influence are not clear.
Methods: Effects of the novel NPY Y5 receptor antagonist L-152,804 on the onset and maintenance of operant self-administration were examined in male C57BL/6J mice, which were trained to self-administer ethanol (10% v/v) versus water via the sucrose substitution method during 16 hr overnight sessions. After 4 months of baseline responding, mice were injected with L-152,804 (0, 10, 30, or 60 mg/kg, intraperitoneally) before operant sessions. Potential locomotor effects of L-152,804 and possible interaction with the sedative properties of ethanol also were examined.
Results: All three doses of L-152,804 significantly delayed the onset of ethanol-reinforced responding relative to vehicle injection. L-152,804 produced no effect on the total number of ethanol- or water-reinforced responses per 16 hr session. However, L-152,804 selectively modulated the temporal distribution of ethanol-reinforced responding depending on the dose (10 and 60 mg/kg) and time point measured in a manner consistent with blockade of ethanol reinforcement. Additional experiments determined that L-152,804 (10 or 60 mg/kg) did not alter spontaneous locomotor activity or influence the sedative effects of ethanol (4 g/kg).
Conclusions: These results indicate that blockade NPY Y5 receptor activity modulates the onset and maintenance of ethanol self-administration. For this reason, NPY-Y5 receptor antagonists may be useful in medical management of alcohol abuse and alcoholism.