Chronic ethanol administration downregulates neurotensin receptors in long- and short-sleep mice

Neurotensin (NT) has been shown to differentially alter many of the physiologic responses to ethanol administration in long-sleep (LS) and short-sleep (SS) mice, which were selectively bred for differences in hypnotic sensitivity to ethanol. These mice have been shown to differ in NT receptor densities in cortical and mesolimbic brain regions and it has been suggested that ethanol actions may be mediated, in part, by neurotensinergic processes. The present study was conducted to further examine this hypothesis by determining the effects of acute and chronic ethanol administration on NT receptor systems in these mice. Scatchard analysis of [3H]NT binding in brain membranes from mice chronically treated with ethanol yielded a one-site model, whereas binding in membranes from control mice were best described by a two-site model. Values for binding capacity (Bmax) were significantly reduced in several brain regions, and binding site density for total, levocabastine-sensitive, and levocabastine-insensitive binding sites were also reduced. The maximum effect was seen after 2 weeks of chronic ethanol consumption. Three weeks after withdrawal from ethanol, Kd and Bmax had returned to control values. Similarly, binding density in all regions for total, levocabastine-sensitive, and levocabastine-insensitive sites had returned to control values within 2 weeks. NT receptor characteristics 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 neurotensin receptor systems further supports the hypothesis that ethanol's actions may be mediated in part by neurotensinergic systems.