EFFECTS OF ADENOSINE-A(1) AND ADENOSINE-A(2) RECEPTOR ACTIVATION ON ELECTRICALLY-EVOKED DOPAMINE AND ACETYLCHOLINE-RELEASE FROM RAT STRIATAL SLICES

The authors investigated how electrically evoked [H-3]dopamine (DA) an d [C-14]acetylcholine (ACh) release in the rat striatum is affected, d irectly or indirectly, by adenosine A1 and A2A receptor activation. St riatal slices, preincubated with [H-3]DA and [C-14] choline, were supe rfused continuously and subjected to electrical field stimulation. The electrically evoked release of both [H-3] and [C-14] was tetrodotoxin sensitive and calcium dependent. The release of both labels was augme nted by haloperidol and sulpiride but only the [C-14]ACh release was i ncreased by tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (each a t 1 muM). The A1 receptor-selective agonist cyclohexyladenosine and th e A2A receptor-selective agonist boxy-methyl)-phenethylamino]-5'-N-eth ylcarboxamido adenosine (CGS 21680) both caused a concentration-depend ent (range, 0.01 - 1 muM) inhibition of electrically evoked DA and ACh release and with a surprisingly similar potency. The potency of both compounds, and particularly of cyclohexyladenosine, increased when the y were allowed to equilibrate for a longer period with the slices. The effect of both compounds was blocked by the A1-selective antagonist 1 ,3-dipropyl-8-cyclopentyl xanthine (0.1 muM). CGS 21680 never caused a ny stimulation of DA or ACh release. The ability of the D2 agonist qui npirole to inhibit ACh release was reduced by CGS 21680 in the presenc e or absence of 0.1 muM 1,3-dipropyl-8-cyclopentyl xanthine. CGS 21680 did not alter the D2 receptor inhibition of DA release. In summary, a denosine analogs inhibit DA and ACh release from rat striatum by a rec eptor that may be different from those hitherto characterized. In addi tion, activation of the adenosine A2A receptor decreases the effect of a D2 receptor agonist on evoked ACh release in the rat striatum. Thus , adenosine may modulate striatal neurotransmission at different sites and through more than one type of receptor.