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Intra‐Amygdala Infusion of the NPY Y1 Receptor Antagonist BIBP 3226 Attenuates Operant Ethanol Self‐Administration
Author(s) -
Schroeder Jason P.,
Olive Foster,
Koenig Heather,
Hodge Clyde W.
Publication year - 2003
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000098875.95923.69
Subject(s) - self administration , amygdala , antagonist , neuropeptide y receptor , medicine , central nucleus of the amygdala , endocrinology , ethanol , agonist , alcohol , neuropeptide , receptor , anesthesia , chemistry , biochemistry , organic chemistry
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.