Magnesium ion augmentation of inhibitory effects of adenosine on dopamine release in the rat striatum

Abstract The effects of adenosine and magnesium ion (Mg²⁺) on striatal dopamine release were studied in awake rats by in vivo microdialysis. The mean striatal basal levels of dopamine release at Mg²⁺ free perfusate were 56.95 ± 5.30 fmol/sample (for 20 min). By varying the Mg²⁺ levels in perfusate from 0 mmol/L to 1, 10 or 40 mmol/L, the dopamine release was inhibited by Mg²⁺ in a level-dependent manner. Perfusion with modified Ringer's solution containing zero Mg²⁺ and from 5 to 50 μmol/L adenosine, non-selective adenosine agonist, as well as 0.1 μmol/L 2-chloro-N⁶-cyclopentyladenosine (CCPA), selective adenosine Al agonist, showed no effect on dopamine release. However, from 5 to 50 μmol/L adenosine and from 0.1 to 1 μmol/L CCPA plus Mg²⁺ (1 and 40 μmol/L) perfusion decreased the dopamine release. This inhibitory effect of adenosine and CCPA on striatal dopamine release was enhanced by an increase in extracellular Mg²⁺ levels. Levels of 50 μmol/L of 8-cyclopentyl-l,3-dimethylxanthine (CPT), a selective adenosine Al receptor antagonist, in perfusate increased the dopamine release under conditions both with and without Mg²⁺. This stimulatory effect of CPT on striatal dopamine release was reduced by an increase in extracellular Mg²⁺ levels. As a result, CPT antagonized the inhibitory effects of adenosine and CCPA on dopamine release under conditions of the presence and absence of Mg²⁺. These results suggest that the inhibition of striatal dopamine release by adenosine was mediated by adenosine Al receptor. This inhibition was intensified by Mg²⁺. This study also revealed that the concentrations of Mg²⁺, which ranged from physiological to supraphysiological, reduced the striatal dopamine release; furthermore it was found that the physiological concentration of Mg²⁺ potentiated the effects of adenosine agonists, but inhibited adenosine antagonist. Thus, the present study, using in vivo microdialysis preparations, suggests Mg²⁺ inhibits the calcium ion channels and enhances the adenosinergic function in the central nervous system.