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 mGlu5 receptor agonist (RS)-2-Cholro-5-Hydroxyphenylglycine (CHPG, 1-6 μg/10 μl 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 A2A 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 D2 receptors for the agonist, an effect potentiated by CGS 21680 (30 nM). These results show the occurrence of functional interactions among mGlu5, adenosine A2A, and dopamine D2 receptors in the regulation of striatal functioning, and suggest that mGlu5 receptors may be regarded as alternative/integrative targets for the development of therapeutic strategies in the treatment of Parkinson's disease.