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 slices and synaptosomes. Recently, a direct interaction between the adenosine A2 receptor and dopamine D2 receptor has been provided. Activation of striatal adenosine A1 receptors is known to partially inhibit the release of dopamine (DA), but some aspects of this mechanism remain unclear. We have studied the participation of adenosine A1 receptors in the control of DA release 'in vivo' in awake, freely moving rats using 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 be 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 data suggest that adenosine acting through A1 receptors possibly localized on striatal dopaminergic nerve terminals can block an induced D2 receptor blockade, but not the releasing effects caused by (+)-amphetamine and high K+ concentration. It is postulated that the increase in DA release by haloperidol is mainly due to an increased firing rate of the DA neurons and that A1 receptor activation can block the DA release observed in response to the action potential activation of DA nerve terminals.
Ballarin
M
M
Unitat de Bioquímica, Facultat de Medicina, Universitat de Barcelona, Spain.
Reiriz
J
J
Ambrosio
S
S
Mahy
N
N
D015762:2-Chloroadenosine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D018047:Receptors, Purinergic P1; D015102:3,4-Dihydroxyphenylacetic Acid; D015762:2-Chloroadenosine; D000661:Amphetamine; D006220:Haloperidol; D011188:Potassium; D004298:Dopamine