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-dependent stimulation of dopamine release. The P2 receptor antagonists reactive blue 2 and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (30 microM each) depressed the basal release of dopamine when given alone and in addition counteracted the stimulatory effect of 2-MeSATP (1 mM). In contrast, a combination of the excitatory amino acid receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 300 microM) and 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 100 microM) increased the basal release of dopamine by themselves and facilitated the effect of 2-MeSATP (1 mM). The results suggest a physiologically relevant regulation of tonic dopamine 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.
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology