Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats.
Activation of central neuropeptide Y (NPY) receptors is known to produce several behavioral effects, including feeding, modulation of memory and antagonism of behavioral effects of stress. In addition, experiments in knock-out and transgenic mice have suggested a possible role of NPY regulation of voluntary ethanol intake. NPY receptors involved in this action are not known. Here, we examined the effects of a selective NPY-Y2 receptor antagonist, BIIE0246, on operant responding for ethanol in a sweetened solution, or the sweetened solution without ethanol, during 30 min sessions of free choice between the two. BIIE0246 produced a robust suppression of responding for ethanol (40% reduction, P=0.013) at an intracerebroventricular dose of 1.0 nmol, but not 0.3 nmol. Responding for the saccharin solution was not significantly affected. The dose range examined was selected since preliminary experiments with doses of 3 nmol and higher indicated sedative effects, but such effects were absent up to 1.0 nmol, as shown by unaffected exploratory locomotor activity. In summary, antagonism at central NPY-Y2 receptors seems to selectively suppress operant self-administration of ethanol. This suggests that Y2 receptors might be candidate targets for developing novel pharmacological treatments of alcoholism.
Thorsell
A
A
Neurotec, Karolinska Institutet, M46, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
Rimondini
R
R
Heilig
M
M
D000428:Alcohol Drinking / Q000188:drug therapy / Q000523:psychology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D012646:Self Administration / Q000523:psychology
D001552:Benzazepines; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D000431:Ethanol; D001120:Arginine; C403256:BIIE 0246