EFFECT OF LOCALLY INFUSED 2-CHLOROADENOSINE, AN A1 RECEPTOR AGONIST, ON SPONTANEOUS AND EVOKED DOPAMINE RELEASE IN RAT NEOSTRIATUM

Adenosine has been shown to inhibit dopamine release from striatal sli ces and synaptosomes. Recently, a direct interaction between the adeno sine A2 receptor and dopamine D2 receptor has been provided. Activatio n of striatal adenosine A1 receptors is known to partially inhibit the release of dopamine (DA), but some aspects of this mechanism remain u nclear. We have studied the participation of adenosine A1 receptors in the control of DA release 'in vivo' in awake, freely moving rats usin g microdialysis. To this end, the effects of 2-chloroadenosine (2-CADO ), a non-metabolizable adenosine A1 receptor agonist, were studied on basal and stimulated striatal DA release. Basal levels were found to b e slightly decreased by a maximal concentration of 2-CADO without any changes in DA metabolites. Haloperidol stimulated DA release was fully counteracted by 2-CADO. However, high K+ (100 mM) or (+)-amphetamine stimulated DA release was not altered by 2-CADO. Altogether, these dat a suggest that adenosine acting through Al receptors possibly localize d on striatal dopaminergic nerve terminals can block an induced D2 rec eptor blockade, but not the releasing effects caused by (+)-amphetamin e and high K+ concentration. It is postulated that the increase in DA release by haloperidol is mainly due to an increased firing rare of th e DA neurons and that A1 receptor activation can block the DA release observed in response to the action potential activation of DA nerve te rminals.