Neurotensin levels in specific brain regions and hypnotic sensitivity to ethanol and pentobarbital as a function of time after haloperidol administration in selectively bred rat lines

Evidence indicates that sensitivity to ethanol is a good predictor of the d evelopment of alcoholism. Thus, identification of neuronal processes that r egulate ethanol sensitivity has been the subject of much recent research. T he present studies were designed to further test the hypothesis that neurot ensinergic processes mediate, in part, hypnotic sensitivity to ethanol. Sin gle doses of haloperidol were administered to lines of rats [selectively br ed for high and low sensitivity (HAS and LAS, respectively) to hypnotic eff ects of ethanol] to produce increases in neurotensin (NT) levels in brain r egions. At 20 h after administration, haloperidol produced dose-dependent i ncreases in NT immunoreactivity, levels in nucleus accumbens (NA) and cauda te putamen (CP) in both HAS and LAS lines. Levels of NT in NA and CP return ed to control values at 48 h after 4 mg/kg haloperidol. These studies used two measures of hypnotic sensitivity to ethanol: duration of loss of righti ng reflex (sleep time) and blood ethanol concentration at regain of rightin g reflex (BECRR). At 20 h, but not 48 h, after haloperidol treatment, both HAS and LAS rats displayed increases in ethanol-induced sleep time with con comitant decreases in BECRR. Pentobarbital-induced sleep time was not incre ased 20 h after administration of 4 mg/kg haloperidol; however, hypnotic se nsitivity to both pentobarbital and ethanol was increased by acute (30-min) pretreatment with 1 mg/kg. These results suggest that NT levels in NA, act ing via NT receptors, enhance hypnotic sensitivity to ethanol, but not pent obarbital.