Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking

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.
Psychopharmacology (Impact Factor: 3.88). 12/2009; 208(3):417-26. DOI: 10.1007/s00213-009-1741-y
Source: PubMed


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.
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.
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.
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.

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    • "Local infusion of a viral vector designed to overexpress NPY into the amygdala reduces alcohol intake [138]. Moreover, NPY blocks the reinstatement of alcohol-seeking induced by yohimbine in rats [139]. The serum levels of adiponectin are significantly elevated in patients with alcohol dependence at admission for alcohol detoxification as well as after one week of withdrawal treatment [140]. "
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