A1 receptors self-regulate adenosine release in the striatum: evidence of autoreceptor characteristics

Adenosine A(1) receptors are inhibitory G-protein coupled receptors that presynaptically regulate neurotransmitter release, but their role in self-regulating adenosine release is not known. In this study, we examined the modulation of evoked adenosine and dopamine efflux by A(1) receptors and studied whether D(1) receptors mediate these effects. Fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used for the simultaneous detection of adenosine and dopamine efflux on a subsecond time scale. Short electrical stimulation trains delivered to the substantia nigra (60 pulses, 60 Hz) were used to evoke dopamine and adenosine release in the striatum. The adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA, 1 mg/kg, i.p.) decreased both adenosine and dopamine efflux, although the effect for adenosine occurred more quickly than for dopamine. The A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 6 mg/kg, i.p.) increased stimulated adenosine release. The effects of CPA were partially attenuated by the dopamine D(1) receptor antagonist SCH-23390. Thus, A(1) and D(1) receptors have a synergistic interaction that modulates both stimulated adenosine and dopamine. The decrease in adenosine is not a downstream effect of lowered dopamine release, as decreasing dopamine synthesis and release with α-methyl-p-tyrosine or increasing release with haloperidol had no effect on adenosine release. This study shows that A(1) receptors have some characteristics of an autoreceptor, including self-regulation of adenosine release.