title: Neurotensin receptor type 1 regulates ethanol intoxication and consumption in mice.
abstract: Neurotensin receptor type 1 (NTS1) is known to mediate a variety of biological functions of neurotensin (NT) in the central nervous system. In this study, we found that NTS1 null mice displayed decreased sensitivity to the ataxic effect of ethanol on the rotarod and increased ethanol consumption when given a free choice between ethanol and tap water containing bottles. Interestingly, the administration of NT69L, a brain-permeable NT analog, increased ethanol sensitivity in wild-type littermates but had no such effect in NTS1 null mice, suggesting that NTS1 contributes to NT-mediated ethanol intoxication. Furthermore, the daily treatment of NT69L, for 4 consecutive days, significantly reduced alcohol preference and consumption in wild-type littermates but had no such effects in NTS1 null mice in a two-bottle drinking experiment. Our study provides evidence for possible pharmacological roles of NT69L in which it increases sensitivity to the ataxic effect, and decreases voluntary consumption, of ethanol. Our study also demonstrates NTS1-mediated behavioral effects of NT69L. Therefore, our findings will be useful for understanding some aspects of alcoholism as well as to develop novel pharmacological therapeutic options for humans.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, College of Medicine, Rochester, MN 55905, USA.
authors.forename: Moonnoh R
authors.initials: MR
authors.lastname: Lee
authors.forename: David J
authors.initials: DJ
authors.lastname: Hinton
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Song
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Christopher
authors.initials: C
authors.lastname: Choo
authors.forename: Heidi
authors.initials: H
authors.lastname: Johng
authors.forename: Sencan S
authors.initials: SS
authors.lastname: Unal
authors.forename: Elliott
authors.initials: E
authors.lastname: Richelson
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018028:Receptors, Neurotensin / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D000431:Ethanol