Methamphetamine increases locomotion and dopamine transporter activity in dopamine d5 receptor-deficient mice

• Published in: PloS one Vol. 8; no. 10; p. e75975
• Main Authors: Hayashizaki, Seiji, Hirai, Shinobu, Ito, Yumi, Honda, Yoshiko, Arime, Yosefu, Sora, Ichiro, Okado, Haruo, Kodama, Tohru, Takada, Masahiko
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.10.2013; Public Library of Science (PLoS)
• Subjects: Amphetamines; Animals; Behavior; Brain; Central nervous system; Cocaine; Dopamine; Dopamine - metabolism; Dopamine D5 receptors; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine receptors; Dopamine transporter; Genotype & phenotype; Locomotion; Locomotion - drug effects; Locomotor activity; Methamphetamine; Methamphetamine - pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurosciences; Phenols (Class of compounds); Phosphorylation; Phosphorylation - drug effects; Receptors; Receptors, Dopamine D5 - deficiency; Receptors, Dopamine D5 - metabolism; Rodents; Science; Stem cells; Threonine; Variance analysis; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0075975

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.