Intra-Amygdala Infusion of the NPY Y1 Receptor Antagonist BIBP 3226 Attenuates Operant Ethanol Self-Administration

Jason P. Schroeder, Foster Olive, Heather Koenig, Clyde W. Hodge

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Background: Neuropeptide Y (NPY) is the most abundant and widely distributed peptide in the mammalian central nervous system. Evidence suggests that NPY transmission at Y1 receptors may regulate alcohol self-administration in rodent models. The purpose of the present study was to test the involvement of NPY Y1 receptors in the amygdala in the reinforcing effects of alcohol. Methods: Long-Evans rats were trained to self-administer ethanol (10% v/v) vs. water on a concurrent FR-1 schedule of reinforcement using a sucrose fading procedure. After a 1 month baseline period, bilateral injector cannulae were surgically implanted to terminate 1 mm dorsal to the central nucleus of the amygdala. Daily (Monday through Friday) operant self-administration sessions were conducted for 6 months after surgery. Then, the effects of intra-amygdala infusion of the high-affinity nonpeptide NPY Y1 receptor antagonist BIBP 3226 (1, 10, or 20 μMg) were determined on parameters of operant alcohol self-administration. Results: Intra-amygdala administration of 10 μM or 20 μM BIBP 3226 decreased total alcohol-reinforced responding and dose of self-administered ethanol (g/kg) without significantly altering total water responses or intake compared with vehicle control. Response onset was unaffected. Analysis of the temporal pattern of ethanol- and water-reinforced responding showed that BIBP 3226 decreased cumulative ethanol-reinforced responding during the 30 to 60 min period of the sessions. Water-reinforced responses were increased by the low dose of BIBP 3226 (1 μM) during the 50 to 60 min period. Conclusions: Results from this study indicate that alcohol-reinforced responding is reduced by acute blockade of NPY Y1 receptors in the amygdala of rats with a long-term history of alcohol self-administration. These data are consistent with the hypothesis that alcohol self-administration is maintained by NPY neurotransmission at Y1 receptors in the central nucleus of the amygdala.

Original languageEnglish (US)
Pages (from-to)1884-1891
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Issue number12
StatePublished - Dec 2003
Externally publishedYes


  • Alcohol Self-Administration
  • Amygdala
  • BIBP 3226
  • Neuropeptide Y
  • Y1 Receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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