Intra-amygdala infusion of the NPY Y1 receptor antagonist BIBP 3226 attenuates operant ethanol self-administration.
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 microMg) were determined on parameters of operant alcohol self-administration.


RESULTS
Intra-amygdala administration of 10 microM or 20 microM 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 microM) 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.
Schroeder
Jason P
JP
Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, 27599, USA.
Olive
Foster
F
Koenig
Heather
H
Hodge
Clyde W
CW
D000428:Alcohol Drinking / Q000517:prevention & control* / Q000523:psychology; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D012646:Self Administration
C092926:BIBP 3226; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D000431:Ethanol; D001120:Arginine