The selective mGlu5 receptor agonist CHPG inhibits quinpirole-induced turning in 6-hydroxydopamine-lesioned rats and modulates the binding characteristics of dopamine D2 receptors in the rat striatum -: Interactions with adenosine A2a receptors

In 6-hydroxydopamine-lesioned rats, the selective mGlu(5) receptor agonist (RS)-2-Cholro-5-Hydroxyphenylglycine (CHPG, 1-6 mug/10 mul intracerebroventricularly) significantly inhibited contralateral turning induced by quinpirole and, to a lesser extent, that induced by SKF 38393. The inhibitory effects of CHPG on quinpirole-induced turning were significantly potentiated by an adenosine A(2A) receptor agonist (CGS 21680, 0.2 mg/kg IP) and attenuated by an A2A receptor antagonist (SCH 58261, 1 mg/kg IP). In rat striatal membranes, CHPG (100-1,000 nM) significantly reduced the affinity of the high-affinity state of D-2 receptors for the agonist, an effect potentiated by CGS 21680 (30 nM), These results show the occurrence of functional interactions among, mGlu(5), adenosine A(2A), and dopamine D-2 receptors in the regulation of striatal functioning, and suggest that mGlu(5) receptors may be regarded as alternative/integrative targets for the development of therapeutic strategies in the treatment of Parkinson's disease.