Abstract
Introduction
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.
Materials and methods
NPY [5.0 or 10.0 μg/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.
Results and discussion
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.
Conclusion
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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Acknowledgements
We thank Dr. Melanie Schwandt and Karen Smith for careful revision of the paper. We are also thankful to Monique Melige for taking care of animal facility and animal housing.
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The authors declare no conflicts of interest.
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Cippitelli, A., Damadzic, R., Hansson, A.C. et al. Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking. Psychopharmacology 208, 417–426 (2010). https://doi.org/10.1007/s00213-009-1741-y
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DOI: https://doi.org/10.1007/s00213-009-1741-y