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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Available from: Anita C Hansson, Oct 07, 2015
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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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    • "During extinction the lever presses were no longer associated with alcohol delivery, but house light was still presented to allow for its concomitant extinction. Stress exposure consisted of the challenge with the pharmacological stressor yohimbine at doses previously shown to produce reinstatement to alcohol seeking in unselected Wistar rats (Le et al., 2005; Marinelli et al., 2007; Cippitelli et al., 2010a). Yohimbine (0.0, 0.625, 1.25, and 2.5 mg/kg) was administered 30 min prior to the 30 min reinstatement session that was conducted under identical condition of extinction sessions. "
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    • "Withdrawal-induced decreases in CeA NPY likely contribute to increased GABAergic tone in alcohol-dependent animals, particularly since application of exogenous NPY normalizes dependence-induced increases in GABA release in CeA (Gilpin et al., 2011). Consistent with this hypothesis, it has been proposed that inhibitory neuronal populations in CeA mediate the ability of ICV NPY to block stressinduced reinstatement of alcohol-seeking behavior (Cippitelli et al., 2010). "
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