Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking.
BACKGROUND
Reinstatement of responding to a previously alcohol-associated lever following extinction is an established model of relapse-like behavior and can be triggered by stress exposure. Here, we examined whether neuropeptide Y (NPY), an endogenous anti-stress mediator, blocks reinstatement of alcohol-seeking induced by the pharmacological stressor yohimbine.


METHODS
NPY [5.0 or 10.0 mug/rat, intracerebroventricularly (ICV)] dose-dependently blocked the reinstatement of alcohol seeking induced by yohimbine (1.25 mg/kg, i.p.) but failed to significantly suppress the maintenance of alcohol self-administration. We then used c-fos expression mapping to examine neuronal activation following treatment with yohimbine or NPY alone or yohimbine following NPY pre-treatment.


CONCLUSIONS
The analysis was focused on a network of structures previously implicated in yohimbine-induced reinstatement, comprised of central (CeA) and basolateral (BLA) amygdala and the shell of the nucleus accumbens (Nc AccS). Within this network, both yohimbine and NPY potently induced neuronal activation, and their effects were additive, presumably indicating activation of excitatory and inhibitory neuronal populations, respectively.


CONCLUSIONS
These results suggest that NPY selectively suppresses relapse to alcohol seeking induced by stressful events and support the NPY system as an attractive target for the treatment of alcohol addiction.
Cippitelli
Andrea
A
Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), 10 Center Dr. 1/5330, Bethesda, MD 20892-1108, USA.
Damadzic
Ruslan
R
Hansson
Anita C
AC
Singley
Erick
E
Sommer
Wolfgang H
WH
Eskay
Robert
R
Thorsell
Annika
A
Heilig
Markus
M
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000378:metabolism / Q000523:psychology*; D000818:Animals; D016739:Behavior, Addictive; D001522:Behavior, Animal; D003216:Conditioning, Operant / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D015016:Yohimbine; D003346:Corticotropin-Releasing Hormone