{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:35:41Z","timestamp":1791300941783,"version":"4.1.0"},"reference-count":35,"publisher":"Society for Neuroscience","issue":"45","license":[{"start":{"date-parts":[[2006,5,9]],"date-time":"2006-05-09T00:00:00Z","timestamp":1147132800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2005,11,9]]},"abstract":"<jats:p>Evidence for heteromeric receptor complexes comprising adenosine A<jats:sub>2A<\/jats:sub>and metabotropic glutamate 5 (mGlu5) receptors in striatum has raised the possibility of synergistic interactions between striatal A<jats:sub>2A<\/jats:sub>and mGlu5 receptors. We investigated the role of striatal A<jats:sub>2A<\/jats:sub>receptors in the locomotor stimulant and antiparkinsonian properties of mGlu5 antagonists using complementary pharmacologic and genetic approaches. Locomotion acutely stimulated by the mGlu5 antagonist [2-methyl-6-(phenylethynyl)-pyridine (MPEP)] was absent in mGlu5 knock-out (KO) mice and was potentiated by an A<jats:sub>2A<\/jats:sub>antagonist KW-6002 [(<jats:italic>E<\/jats:italic>)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine], both in normal and in dopamine-depleted (reserpinized) mice. Conversely, the MPEP-induced motor response was markedly attenuated in single and double A<jats:sub>2A<\/jats:sub>and D<jats:sub>2<\/jats:sub>receptor KO mice. In contrast, motor stimulation by a D<jats:sub>1<\/jats:sub>dopamine agonist was not attenuated in the KO mice. The A<jats:sub>2A<\/jats:sub>receptor dependence of MPEP-induced motor stimulation was investigated further using a postnatal forebrain-specific conditional (Cre\/<jats:italic>loxP<\/jats:italic>system) KO of the A<jats:sub>2A<\/jats:sub>receptor. MPEP loses the ability to stimulate locomotion in conditional KO mice, suggesting that this mGlu5 antagonist effect requires the postdevelopmental action of striatal A<jats:sub>2A<\/jats:sub>receptors. The potentiation of mGlu5 antagonist-induced motor stimulation by an A<jats:sub>2A<\/jats:sub>antagonist and its dependence on both D<jats:sub>2<\/jats:sub>and forebrain A<jats:sub>2A<\/jats:sub>receptors highlight the functional interdependence of these receptors. These data also strengthen a rationale for pursuing a combinational drug strategy for enhancing the antiparkinsonian effects of A<jats:sub>2A<\/jats:sub>and mGlu5 antagonists.<\/jats:p>","DOI":"10.1523\/jneurosci.3660-05.2005","type":"journal-article","created":{"date-parts":[[2005,11,10]],"date-time":"2005-11-10T00:53:04Z","timestamp":1131583984000},"page":"10414-10419","source":"Crossref","is-referenced-by-count":105,"title":["Interactions between Metabotropic Glutamate 5 and Adenosine A<sub>2A<\/sub>Receptors in Normal and Parkinsonian Mice"],"prefix":"10.1523","volume":"25","author":[{"given":"Anil","family":"Kachroo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianna R.","family":"Orlando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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