CHRONIC ETHANOL ADMINISTRATION DOWN-REGULATES NEUROTENSIN RECEPTORS IN LONG-SLEEP AND SHORT-SLEEP MICE

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.