title: Methamphetamine increases locomotion and dopamine transporter activity in dopamine d5 receptor-deficient mice.
abstract: Dopamine regulates the psychomotor stimulant activities of amphetamine-like substances in the brain. The effects of dopamine are mediated through five known dopamine receptor subtypes in mammals. The functional relevance of D5 dopamine receptors in the central nervous system is not well understood. To determine the functional relevance of D5 dopamine receptors, we created D5 dopamine receptor-deficient mice and then used these mice to assess the roles of D5 dopamine receptors in the behavioral response to methamphetamine. Interestingly, D5 dopamine receptor-deficient mice displayed increased ambulation in response to methamphetamine. Furthermore, dopamine transporter threonine phosphorylation levels, which regulate amphetamine-induced dopamine release, were elevated in D5 dopamine receptor-deficient mice. The increase in methamphetamine-induced locomotor activity was eliminated by pretreatment with the dopamine transporter blocker GBR12909. Taken together, these results suggest that dopamine transporter activity and threonine phosphorylation levels are regulated by D5 dopamine receptors.
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan ; Japan Science and Technology Agency, CREST, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hayashizaki
authors.forename: Shinobu
authors.initials: S
authors.lastname: Hirai
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ito
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Honda
authors.forename: Yosefu
authors.initials: Y
authors.lastname: Arime
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Haruo
authors.initials: H
authors.lastname: Okado
authors.forename: Tohru
authors.initials: T
authors.lastname: Kodama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takada
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects; D050641:Receptors, Dopamine D5 / Q000172:deficiency* / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050641:Receptors, Dopamine D5; D008694:Methamphetamine; D004298:Dopamine