Possible Interaction: Ethanol and Neuropeptide Y

“Both ethanol exposure and withdrawal from chronic ethanol have been shown to produce changes in NPY and NPY receptor protein levels and mRNA expression in the CNS.”

“Importantly, manipulations of NPY Y1 and Y2 receptor signaling have been shown to alter ethanol consumption and self-administration in a brain region-specific manner, with Y1 receptor activation and Y2 receptor blockade in regions of the extended amygdala promoting robust reductions of ethanol intake.”

“There is a long history of research implicating a role for NPY in modulating neurobiological responses to alcohol (ethanol) as well as other drugs of abuse.”

“Furthermore, recent evidence suggests that NPY has a significant role in the neurobiological response to alcohol , including alcohol consumption, dependence, and withdrawal.”

“Evidence suggesting possible mechanism(s) by which NPY signaling modulates ethanol consumption are considered.”

“Here, we provide an overview of physiological, pharmacological, … genetic research showing that: (A) administration of ethanol , as well as … withdrawal, alter central NPY expression, (B) NPY modulates ethanol consumption under certain conditions, and (C) NPY signaling modulates the sedative effects of several drugs, including ethanol, sodium pentobarbital, and ketamine.”

“It is suggested that NPY may influence ethanol consumption by regulating basal levels of anxiety, by modulating the sedative effects of ethanol, and/or by modulating ethanol's rewarding properties.”

“It appears that increases in CRF contribute to the negative affective state that is strongly associated with alcohol withdrawal, and NPY provides a motivational basis to consume alcohol because the anxiolytic effects of alcohol, which are strongly associated with relapse, appear to be regulated in part by this neuropeptide.”

“The CREB gene transcription factor regulates the expression of the gene encoding neuropeptide Y (NPY), and decreased concentrations of NPY are implicated in anxiety and alcohol drinking behaviors.”

“BACKGROUND In a previous study, neuropeptide Y (NPY) administered into the lateral ventricles decreased ethanol intake in alcohol-preferring (P) rats but not in alcohol-nonpreferring (NP) or unselected Wistar rats.”

“Based on these findings, one might predict that the rewarding effects of alcohol would be blunted in NPY mutant mice.”

“Previous research reported an inverse association between ethanol drinking and cerebral neuropeptide Y (NPY) levels.”

“One theme that emerges from these reviews is that acute and chronic ethanol exposure alter the actions of a number of neurotransmitters and neuromodulators, including γ-aminobutyric acid (GABA), glutamate, dopamine, serotonin and neuropeptides such as dynorphin, corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY) in extended amydala circuitry.”

“Several lines of evidence suggest a possible involvement of the NPY system in the physiological effects of several classes of abused substances including alcohol , phencyclidine, cocaine, and marijuana and in endogenous psychosis.”