Dopaminergic-cholinergic interactions in the striatum: the critical significance of calcium concentrations in brain microdialysis

Summary Brain microdialysis experiments were performed to assess the effects of calcium (1.2 mmol/l and 3.4 mmol/l) in the perfusio solution on a variety of pharmacological treatments known to affect the release of dopamine (DA) and/or acetylcholine (ACh). Intrastriatal infusion of the muscarinic receptor agonist oxotremorine (100 M), the selective dopamine D-2 receptor agonist (–)-N-0437 (1 M), and the indirect DA agonists (+)amphetamine (10 M) and nomifensine (1 M) via the dialysis probe did not affect the overflow of ACh when the perfusion fluid contained 3.4 mmol/l calcium. In contrast, these compounds produced pronounced decreases in the overflow of ACh at 1.2 mmol/l calcium. Intrastriatal infusion of the muscarinic receptor antagonist atropine (1 M) increased the output of ACh both at 1.2 mmol/l and 3.4 mmol/1 calcium. The selective DA D-2 receptor antagonist (–)-sulpiride (1 M) did not affect the overflow of ACh at either calcium concentration. Infusion of oxotremorine and atropine had no effect on the overflow of DA at either 1.2 mmol/l or 3.4 mmol/l calcium. (–)-N-0437 decreased and (–)-sulpirde increased DA overflow, both effects being independent of the calcium concentration in the perfusion fluid. Nomifensine and (–)amphetamine caused relatively (but not absolutely) larger increases in the overflow of DA at 1.2 mmol/1 calcium. These findings emphasize the critical importance of the calcium concentration of the perfusion fluid in determining the nature of pharmacological responses in microdialysis experiments, and demonstrate that locally applied dopaminergic drugs can modulate striatal cholinergic function.Part of these results have been presented in Nottingham at the fourth meeting for Electrochemical detection, HPLC and in vivo monitoring in the biosciencesSend offprint requests to G. Damsma at the present address