Purinergic regulation of brain catecholamine neurotransmission: In vivo electrophysiology and microdialysis study in rats

摘要

It was previously reported that adenosine-2A (A(2A)) receptors interact with dopamine-2 (D-2) receptors on a molecular level. The aim of the current study was to investigate the functional output of this interaction. In vivo microdialysis was used to assess the effects of an antagonist of A(2A) receptors, ZM 241385, and an antagonist of D-2 receptors haloperidol, either alone or in combination, on brain catecholamine levels. It was found that ZM 241385 did not alter catecholamine levels by its own, but potentiated haloperidol-induced dopamine and norepinephrine release in the nucleus accumbens and prefrontal cortex, respectively. In vivo electrophysiology was used to assess the effect of an agonist (CGS 216820) and an antagonist (ZM 241385) of A(2A) receptors on the excitability of dopamine and norepinephrine neurons. It was found that CGS 216820 dose-dependently inhibited dopamine and norepinephrine neurons and ZM 241385 reversed this inhibition. In conclusion, those A(2A) receptors modulate brain catecholamine transmission, and this modulation is mediated, at least in part, via the regulation of excitability of norepinephrine and dopamine neurons. The ability of antagonists of A(2A) receptors to potentiate the effect of haloperidol on brain norepinephrine and dopamine levels may enhance its clinical efficacy as an antipsychotic drug.