Adenosine A2a receptor-mediated modulation of striatal acetylcholine release in vivo

To determine the functions of striatal adenosine A2a receptors in vivo, the effects of a selective agonist, 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamidoaden osi ne hydrochloride (CGS 21680), and an antagonist, (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837), on acetylcholine release were investigated in the striatum of awake freely moving rats using microdialysis. Intracerebroventricular injection of CGS 21680 (10 micrograms) increased acetylcholine release in striatum and KF17837 (30 mg/kg p.o.) antagonized the CGS 21680-induced acetylcholine elevation. To investigate the contribution of dopaminergic and GABAergic neurons on A2a receptor-mediated acetylcholine release, the effects of CGS 21680 were studied by using dopamine-depleted rats in the presence or absence of GABA antagonists. In the dopamine-depleted striatum, the intrastriatal application of CGS 21680 (0.3-30 microM) increased extracellular acetylcholine, which was significantly greater than that in normal striatum. The CGS 21680-induced elevation of acetylcholine release was still observed in the presence of GABA antagonists bicuculline (30 microM) and 2-hydroxysaclofen (100 microM) and was similar in both normal and dopamine-depleted striatum. These results suggest that A2a agonist stimulates acetylcholine release in vivo, and this effect of A2a agonist is modulated by dopaminergic and GABAergic neurotransmission.