Effects of unilateral stimulation of selective striatal dopamine receptors on cerebral metabolism in the rat

Patterns of changes of metabolic and biochemical parameters associated with lesion of the nigrostriatal pathway have been encompassed into a model describing the functional organization of the basal gan-glia circuitry. The model outlines two pathways connecting the striatum to the output nuclei of the circuit: a direct pathway originating from neurons bearing dopamine DI receptors, and an indirect one, originating from neurons expressing Ü2 receptors. The entity of the functional segregation of the two pathways, however, is uncertain and has been recently disputed. In this study, we sought to address this issue by evaluating the functional changes associated with selective pharmacological manipulation of D] and/or Ü2 striatal receptors in freely moving rats. The study was carried out in Sprague-Dawley rats by using the [l4C]-2-deoxyglucose method for measuring local cerebral metabolic rates for glucose. Guide cannulas were implanted in the right striatum (stereotaxic coordinates: AP = +0.7 mm; ML = +2.6 mm; DV =- 4.5 mm). After a week, animals received a unilateral, intrastriatal injection of a DI agonist (SKF-38393, 50 nmoles), a D2 agonist (quinpirole, 39 nmoles), amphetamine (41 nmoles), or vehicle. Drug or vehicle solutions were infused 3 min before the beginning of the procedure for measuring glucose, at a rate of 0.2 ul/min for 2.5 min. Both DI and D2 agonists caused metabolic asymmetries in selected brain areas, including globus pallidus, substantia nigra reticulata and entopeduncular nucleus. Amphetamine - which activates both DI and D? receptors by stimulating the release of endogenous dopamine - caused a similar pattern of metabolic changes, but the effect was occasionally higher than observed with the selective agonist drugs. These results show that stimulation of DI or D2 striatal receptors causes functional changes in all the projection nuclei of the striatum. Our findings are therefore consistent with the reports questioning the functional segregation of the two pathways.