Role of Adenylate Cyclase in the Modulation of the Release of Dopamine: A Microdialysis Study in the Striatum of the Rat

Abstract

In the present study, we have applied the brain microdialysis technique to investigate the effect of the stimulation of adenylate cyclase in the extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of freely moving rats. Infusion of 8-bromo-adenosine 3'',5''-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine, or forskolin produced a significant increase in the release of DA. The effect of 8-Br-cAMP was tetrodotoxin, Ca2+, and dose dependent and was saturable. 8-Br-cAMP also caused an increase in the output of DOPAC and HVA. No effects were seen on the output of 5-HIAA, except at the highest 8-Br-cAMP concentration studied. Infusion of 8-Br-cAMP (25 .mu.M, 1.0 mM, and 3.3 mM) together with infusion of (-)-sulpiride (1 .mu.M) or systemic administration of (.+-.)-sulpiride (55 .mu.mol/kg i.p.) produced an additive effect on the release of DA. Infusion or peripheral administration of (-)-N-0437 (1 .mu.M or 1 .mu.mol/kg) both decreased the 8-Br-cAMP-induced increase in the release of DA. These results demonstrate that cyclic AMP may stimulate the release of DA, but it is unlikely that this second messenger is linked to presynaptic D2 receptors controlling the release of DA.