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TitleD1 dopamine receptor coupling to PLCβ regulates forward locomotion in mice.
Publication TypeJournal Article
Year of Publication2013
AuthorsMedvedev, Ivan O., Amy J. Ramsey, Shababa T. Masoud, Marie Kristel Bermejo, Nikhil Urs, Tatyana D. Sotnikova, Jean-Martin Beaulieu, Raul R. Gainetdinov, and Ali Salahpour
JournalJ Neurosci
Date Published2013 Nov 13
KeywordsAnimals, Female, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Phospholipase C beta, Protein Binding, Receptors, Dopamine D1

Several studies have reported the coupling of dopamine signaling to phospholipase C β (PLCβ) both in vitro and in vivo. However, the precise physiological relevance of this signaling pathway in mediating dopamine behaviors is still unclear. Here we report that stimulation of dopamine receptor signaling in vivo with systemic administration of apomorphine, amphetamine, and cocaine leads to increased production of inositol triphosphate (IP3) in the mouse striatum. Using selective antagonists and dopamine D1 and D2 receptor knock-out animals, we show that the production of IP3 is mediated by the D1 receptor, but not the D2 receptor. A selective blocker of PLCβ, U73122, was used to assess the physiological relevance of D1-mediated IP3 production. We show that U73122 inhibits the locomotor-stimulating effects of apomorphine, amphetamine, cocaine, and SKF81297. Furthermore, U73122 also suppresses the spontaneous hyperactivity exhibited by dopamine transporter knock-out mice. Importantly, the effects of U73122 are selective to dopamine-mediated hyperactivity, as this compound does not affect hyperactivity induced by the glutamate NMDA receptor antagonist MK801. Finally, we present evidence showing that an imbalance of D1- and D2-mediated signaling following U73122 treatment modifies the locomotor output of animals from horizontal locomotor activity to vertical activity, further highlighting the importance of the PLCβ pathway in the regulation of forward locomotion via dopamine receptors.

Alternate JournalJ. Neurosci.
PubMed ID24227722
PubMed Central IDPMC3828465
Grant List1K99ES016816-01 / ES / NIEHS NIH HHS / United States
210296 / / Canadian Institutes of Health Research / Canada
258294 / / Canadian Institutes of Health Research / Canada