Adenosine 5 '-triphosphate-induced dopamine release in the rat nucleus accumbens in vivo

Microdialysis experiments were used to investigate the influence of locally applied 2-methylthioadenosine 5'-triphosphate (2-MeSATP) on extracellular dopamine concentrations in the rat nucleus accumbens (NAc). 2-MeSATP (0.1, 1, 10 mM) infused via the microdialysis probe caused a concentration-depend ent stimulation of dopamine release. The P2 receptor antagonists reactive b lue 2 and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (30 mu M each) depressed the basal release of dopamine when given alone and in addition counteracted the stimulatory effect of 2-MeSATP (1 mM). In contra st, a combination of the excitatory amino acid receptor antagonists 6-cyano -7-nitroquinoxaline-2,3-dione (CNOX; 300 mu M) and 3-((RS)-2-carboxypiperaz in-4-yl)-propyl-1-phosphonic acid (CPP; 100 mu M) increased the basal relea se of dopamine by themselves and facilitated the effect of 2-MeSATP (1 mM). The results suggest a physiologically relevant regulation of tonic dopamin e release in the NAc by endogenous ATP via P2 receptors. This is due to the combination of a direct and an indirect (via glutamate release) effect of ATP on mesolimbic dopaminergic neurons. (C) 1999 Elsevier Science Ireland L td. All rights reserved.