Ad. Campbell et Vg. Erwin, CHRONIC ETHANOL ADMINISTRATION DOWN-REGULATES NEUROTENSIN RECEPTORS IN LONG-SLEEP AND SHORT-SLEEP MICE, Pharmacology, biochemistry and behavior, 45(1), 1993, pp. 95-106
Neurotensin (NT) has been shown to differentially alter many of the ph
ysiologic responses to ethanol administration in long-sleep (LS) and s
hort-sleep (SS) mice, which were selectively bred for differences in h
ypnotic sensitivity to ethanol. These mice have been shown to differ i
n NT receptor densities in cortical and mesolimbic brain regions and i
t has been suggested that ethanol actions may be mediated, in part, by
neurotensinergic processes. The present study was conducted to furthe
r examine this hypothesis by determining the effects of acute and chro
nic ethanol administration on NT receptor systems in these mice. Scatc
hard analysis of [H-3]NT binding in brain membranes from mice chronica
lly treated with ethanol yielded a one-site model, whereas binding in
membranes from control mice were best described by a two-site model. V
alues for binding capacity (B(max)) were significantly reduced in seve
ral brain regions, and binding site density for total, levocabastine-s
ensitive, and levocabastine-insensitive binding sites were also reduce
d. The maximum effect was seen after 2 weeks of chronic ethanol consum
ption. Three weeks after withdrawal from ethanol, K(d) and B(max) had
returned to control values. Similarly, binding density in all regions
for total, levocabastine-sensitive, and levocabastine-insensitive site
s had returned to control values within 2 weeks. NT receptor character
istics measured 2 h post-3.0 g/kg ethanol revealed that ethanol caused
a rapid downregulation of both subtypes of NT receptors. The finding
that both acute and chronic ethanol significantly downregulate the neu
rotensin receptor systems further supports the hypothesis that ethanol
's actions may be mediated in part by neurotensinergic systems.