Activation of A1 adenosine receptors decreases the release of serotonin in the rabbit hippocampus, but not in the caudate nucleus.

The effects of A1 adenosine receptor ligands on the evoked release of serotonin (5-HT) were studied in slices of the hippocampus and the caudate nucleus of the rabbit, preincubated with 3H-5-HT. In hippocampal tissue electrical stimulation elicited a release which was inhibited by the adenosine receptor agonist N6-cyclohexyladenosine (CHA) and enhanced by the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The concentration-response curve of CHA was shifted to the right by DPCPX. The shift corresponded to a pA2 value of 9.4 for DPCPX. CHA, R-N6-phenylisopropyladenosine (R-PIA) and DPCPX were ineffective in caudate nucleus tissue. When instead of electrical pulses high K+ was used to induce 5-HT release in the presence of the Na+ channel blocker tetrodotoxin (TTX), which was present in order to exclude effects mediated by interneurones, CHA was equally effective in the hippocampus but again failed to modify 5-HT release in the caudate nucleus. The disinhibition by DPCPX of the evoked 5-HT release was used to calculate the extracellular concentration of endogenous adenosine at the A1 receptor. The calculation greatly depended on the dissociation constant of adenosine at the A1 receptor. It is concluded that A1 adenosine receptors, activated by the endogenous agonist at a concentration of about 0.7 mumol/l, are located on serotonergic nerve endings in the hippocampus, but not in the caudate nucleus. The estimated extracellular concentration of endogenous adenosine is in reasonable agreement with actually measured concentrations reported in the literature.