title: Dopaminergic transmission in STOP null mice.
abstract: Neuroleptics are thought to exert their anti-psychotic effects by counteracting a hyper-dopaminergic transmission. Here, we have examined the dopaminergic status of STOP (stable tubule only polypeptide) null mice, which lack a microtubule-stabilizing protein and which display neuroleptic-sensitive behavioural disorders. Dopamine transmission was investigated using both behavioural analysis and measurements of dopamine efflux in different conditions. Compared to wild-type mice in basal conditions or following mild stress, STOP null mice showed a hyper-locomotor activity, which was erased by neuroleptic treatment, and an increased locomotor reactivity to amphetamine. Such a behavioural profile is indicative of an increased dopaminergic transmission. In STOP null mice, the basal dopamine concentrations, measured by quantitative microdialysis, were normal in both the nucleus accumbens and the striatum. When measured by electrochemical techniques, the dopamine efflux evoked by electrical stimulations mimicking physiological stimuli was dramatically increased in the nucleus accumbens of STOP null mice, apparently due to an increased dopamine release, whereas dopaminergic uptake and auto-inhibition mechanisms were normal. In contrast, dopamine effluxes were slightly diminished in the striatum. Together with previous results, the present study indicates the association in STOP null mice of hippocampal hypo-glutamatergy and of limbic hyper-dopaminergy. Such neurotransmission defects are thought to be central to mental diseases such as schizophrenia.
authors.affiliation: Institut Fédératif des Neurosciences de Lyon; UCBL, Faculté de Pharmacie, Laboratoire de Neuropharmacologie et Neurochimie, Lyon, France. pbrun@sante.univ-lyon1.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Brun
authors.forename: Mélina
authors.initials: M
authors.lastname: Bégou
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.forename: Laurence
authors.initials: L
authors.lastname: Mouly-Badina
authors.forename: Magali
authors.initials: M
authors.lastname: Clerget
authors.forename: Annie
authors.initials: A
authors.lastname: Schweitzer
authors.forename: Hélène
authors.initials: H
authors.lastname: Scarna
authors.forename: Bernard
authors.initials: B
authors.lastname: Renaud
authors.forename: Didier
authors.initials: D
authors.lastname: Job
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Suaud-Chagny
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D003624:Darkness; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D008027:Light; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; D009419:Nerve Tissue Proteins; D004298:Dopamine