Direct, real-time assessment of dopamine release autoinhibition in the rat caudate–putamen

Abstract

Inhibition of endogenous dopamine release by photo-released dopamine (i.e., autoinhibition) was characterized in the rat caudate–putamen using combined caged-dopamine photolysis and fast-scan cyclic voltammetry. Coronal brain slices (400 μm thick) were perfused with caged-dopamine (150–200 μM in artificial cerebrospinal fluid). Ultraviolet illumination of increasing duration (25–250 ms, ∼100 μm beam diameter) was focused at the tip of the recording electrode to uncage increasing amounts of exogenous dopamine at the recording sites (0.5–5 μM); a single biphasic electrical stimulus was delivered 0.1–10 s later to induce endogenous dopamine release. The concentrations of both endogenous and exogenous dopamine were determined using voltammetry, thus enabling determination of concentration-dependent inhibition of the endogenous release by the latter. While unaffected by control ultraviolet illumination, endogenous dopamine release was rapidly inhibited by photo-released dopamine in a concentration-dependent manner. Photo-application of 3–5 μM exogenous dopamine inhibited the endogenous release by 90–100% (electrical stimulus applied 1 s after photolysis initiation), an effect prevented by 2 μM sulpiride. The autoinhibition was dependent on the time between photolysis onset and electrical stimulation. Terminal dopamine autoreceptor stimulation led to robust inhibition of endogenous dopamine release with a latency of ∼200 ms and effective duration of less than 5 s. The percent autoinhibition was a skewed, U-shaped function of photolysis/electrical stimulation intervals with the peak inhibition at 1 s. This study directly demonstrates that autoreceptor-mediated inhibition of terminal dopamine release in caudate–putamen is designed to provide a rapid, robust, yet short-lasting modulation of terminal dopamine release.