Cl. Ehlers et al., NEUROPEPTIDE-Y LEVELS IN ETHANOL-NAIVE, ALCOHOL-PREFERRING, AND NONPREFERRING RATS AND IN WISTAR RATS AFTER ETHANOL EXPOSURE, Alcoholism, clinical and experimental research, 22(8), 1998, pp. 1778-1782
Neuropeptide Y (NPY) is a hexatriacontapeptide amide that is now well
characterized as a neuromodulator in the central nervous system (CNS),
When infused into the CNS, NPY produces both anxiolytic end orexigeni
c effects. NPY's anxiolytic effects appear to be mediated through rece
ptors in the central amygdala, whereas its orexigenic effects are loca
lized in discrete hypothalamic nuclei. Both food restriction and food
deprivation produce increased revels of the peptide in the hypothalamu
s that are ameliorated by refeeding. However, the effects of alcohol c
onsumption/deprivation on NPY levels remain unknown. The present study
sought to determine if brain NPY levels were affected by either alcoh
ol exposure and/or correlated with genetic differences in preference f
or drinking alcohol. In the first experiment, NPY-like immunoreactivit
y (NPY-LI) was compared in alcohol-naive, alcohol-preferring (P), and
nonpreferring (NP) rats. After tissue extraction, NPY-LI was measured
by radioimmunoassay: amygdala, hippocampus, frontal cortex, hypothalam
us, and caudate. P rats were found to have significantly lower NPY-LI
in amygdala (F = 4.69, p < 0.04), hippocampus (F = 7.03, p < 0.01), an
d frontal cortex (F = 4.7, p < 0.04), compared with NP rats. In the se
cond experiment, heterozygous Wistar rats were exposed to alcohol for
14 hr/day for 7 weeks in alcohol vapor chambers (mean blood alcohol co
ncentrations = 180 mg%) or control chambers. At 7 weeks of alcohol exp
osure, no significant changes in NPY-LI in were found. At 1 month afte
r ethanol withdrawal, however, the ethanol-exposed animals had signifi
cantly higher NPY-LI in the hypothalamus (F = 4.78, p < 0.04) when com
pared with the nonexposed controls. Taken together, these studies sugg
est that exposure to chronic ethanol may affect NPY-LI at the level of
the hypothalamus in a fashion similar to food restriction, because 4
weeks after alcohol withdrawal, significantly higher NPY levels are fo
und. In addition, differences in NPY-LI in limbic areas and frontal co
rtex between alcohol-naive P and NP rats suggest that NPY may also pla
y a role in risk for the development of alcohol preference either by m
odulating the ''tension-reduction'' properties of alcohol or by influe
ncing consummatory behaviors.