A widely cited model describing the functional organization of the basal ganglia outlines two pathways connecting the striatum to the output nuclei: a "direct" pathway originating from neurons bearing D1 receptors and an "indirect" one from D2 neurons. The entity of the functional segregation of the two pathways, however, is uncertain. In this study we sought to address this issue by evaluating the functional changes associated with selective pharmacological manipulation of D1 and D2 striatal receptors. The study was carried out in freely moving rats by using the 14[C]-2deoxyglucose method for measuring local cerebral metabolic rates for glucose, or Fos immunocytochemistry. Animals received intrastriatal injection of SKF 38393, 29 mM (n = 8); quinpirole, 20 mM (n = 8); amphetamine, 30 mM (n = 7); apomorphine, 3 mM (n = 4 ), or vehicle (n = 9). Infusion (0.2 μ1/min for 2.5 min) started 3 min before the beginning of the procedure for measuring glucose utilization or 2 h before killing the animals for Fos-ir. Coordinates of the pre-implanted cannula were: anterior-posterior, +0.7 mm; medial-lateral, 2.6 mm; dorsal-ventral, -4.5 mm.). The results show that both the selective D1 and D2 agonists modify glucose utilization in selected brain areas, including the globus pallidus, substantia nigra reticulata and entopeduncular nucleus. Amphetamine caused a similar pattern of metabolic change, but the effect was occasionally higher than observed with the selective agonist drugs. The intrastriatal injection of vehicle per se reduced glucose metabolism in cortical regions surrounding the cannula and in thalamic and striatal areas. SKF 38393 or amphetamine caused Fos-ir staining throughout the entire cerebral cortex ipsilateral to the injection site, particularly in the pyriform cortex. Conversely, quinpirole did not cause cortical expression, with the exception of the pyriform cortex. Main finding of the study is the similarity of the functional changes caused by the D1 and D2 selective agonists. Our results further support the hypothesis that, in spite of the anatomical, prevalent segregation of the two families of dopamine receptors, the direct and indirect pathways are not functionally separated. The findings are consistent with a number of reports questioning the functional segregation of the two pathways. The marked difference in the cortical expression of the Fos protein in response to the selective stimulation of striatal D1 or D2 receptors may reflect D1-induced plastic changes occurring at the level of the cortico-striatal synapses.
|Issue number||4 SUPPL.|
|Publication status||Published - 2000|
ASJC Scopus subject areas
- Clinical Neurology