LOCAL MODULATION OF HIPPOCAMPAL ACETYLCHOLINE-RELEASE BY DOPAMINE D1 RECEPTORS - A COMBINED RECEPTOR AUTORADIOGRAPHY AND IN-VIVO DIALYSIS STUDY

The modulation of in vivo hippocampal ACh release by dopaminergic D1 a nd D2 receptors was examined in this study, Additionally, in an attemp t to ascertain the location of these receptors in relation to hippocam pal cholinergic terminals, fimbriaectomy and quantitative autoradiogra phy were used, Following unilateral fimbriaectomy, whereby at least 50 % of hippocampal cholineacetyltransferase (ChAT) activity was lost, a significant ipsilateral decrease in D1/H-3 SCH23390 binding was observ ed in the molecular layer of the dentate gyrus while hippocampal D2/H- 3 raclopride binding was unaffected. The effects of prototypical D1 an d D2 receptor agonists and antagonists on hippocampal ACh release were examined next using in vivo dialysis in freely moving rats. The D1 ag onist SKF 38393 (10 mu M to 100 mu M) administered directly into the h ippocampus via the dialysis probe stimulated ACh release in a concentr ation dependent manner. The effect of the agonist was blocked by the c oadministration of the D1 receptor antagonist SCH 23390 (1 mu M), whic h by itself failed to modulate ACh release. In contrast, neither the D 2 agonist quinpirole (1-10 mu M) nor the D2 antagonist sulpiride (1-10 mu M) had any direct effect on hippocampal ACh release. Additionally, the infusion of these D1 and D2 drugs in the septal area failed to af fect hippocampal ACh release. Taken together, these results suggest th at a proportion of hippocampal D1 receptors are located On cholinergic nerve terminals and that dopamine, acting via D1 receptors, can local ly stimulate hippocampal ACh release.