Overexpression of Neuropeptide Y in the Central Nucleus of the Amygdala Decreases Ethanol Self-administration in “Anxious” Rats

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Neuropeptide Y (NPY) has been implicated in a variety of behaviors including those associated with anxiety and ethanol administration. The current experiment investigated the predictive role of anxiety-like behaviors in ethanol self-administration and the relationship of NPY in the central nucleus of the amygdala (CeA) with anxiety and ethanol self-administration.


Rats were divided into anxious and nonanxious groups based on behavior in the elevated plus maze. Following elevated plus maze testing, rats were allowed to consume increasing concentrations of ethanol (2, 4, and 6%) in a 2-bottle choice procedure over a period of 31 days. anxious rats showed an increased preference for 4% ethanol and 6% ethanol compared with non-anxious rats. Following 20-day access to 6% ethanol, rats underwent gene transfer surgery with replication-defective recombinant herpes simplex 1 vectors encoding prepro-NPY, an antisense NPY RNA, or LacZ (control) into the CeA.


In anxious rats, bilateral injections into the CeA with the NPY-antisense vector increased 6% ethanol preference, while the vector encoding NPY decreased 6% ethanol preference. Herpes simplex viral-mediated alterations in CeA NPY expression did not alter ethanol preference in nonanxious rats.


These results suggest that virally mediated alterations in NPY levels in the CeA differentially affect ethanol consumption in rats with low and high basal levels of anxiety.

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