title: Specific involvement of neurotensin type 1 receptor in the neurotensin-mediated in vivo dopamine efflux using knock-out mice.
abstract: Abstract Neurotensin is a tridecapeptide neurotransmitter known to be involved in psychiatric disorders, various physiological processes and several different neurobiological mechanisms, including modulation of accumbal dopamine release. Two neurotensin extracellular binding sites, namely NT1- and NT2-receptor (NT1R and NT2R), have been cloned from the rat brain. These receptors are distinguishable by their different in vitro pharmacological properties but the available pharmacological tools have weak in vivo potency and specificity. The use of genetically engineered knock-out mice has provided a powerful alternative to the classical pharmacological approach to investigate their respective roles. In this study, using in vivo differential pulse amperometry, we show that, in wild-type mice, neurotensin application into the ventral tegmental area dose-dependently evokes dopamine efflux in the nucleus accumbens. This neurotensin-mediated efflux is dramatically decreased in mice lacking NT1R while it is unaffected in NT2R-deleted mice. This finding indicates that a large part of the dopamine efflux evoked by neurotensin in the nucleus accumbens of wild-type mice is mediated via NT1R present in the ventral tegmental area.
authors.affiliation: INSERM U 512, Laboratoire de Neuropharmacologie et Neurochimie, Institut Fédératif des Neurosciences de Lyon, Faculté de Pharmacie, UCBL, Lyon, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Leonetti
authors.forename: Philippe
authors.initials: P
authors.lastname: Brun
authors.forename: Magali
authors.initials: M
authors.lastname: Clerget
authors.forename: Régis
authors.initials: R
authors.lastname: Steinberg
authors.forename: Philippe
authors.initials: P
authors.lastname: Soubrié
authors.forename: Bernard
authors.initials: B
authors.lastname: Renaud
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Suaud-Chagny
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D004567:Electrodes, Implanted; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism*; D013238:Stereotaxic Techniques; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; C490984:Ntsr2 protein, mouse; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D016202:N-Methylaspartate; D004298:Dopamine