Dopamine Autoreceptors Modulate Dopamine Release from the Prefrontal Cortex

Abstract: Electrical stimulation (at 0.3, 1, or 10 Hz, 120 pulses each) produced a calcium‐dependent overflow of radioactivity from slices of the rabbit prefrontal cortex preloaded with [3H]3,4‐dihydroxyphenylethylamine ([3H]DA, [3H]dopamine) in the presence of desipramine. Flat frequency‐release curves were observed. Apomorphine and LY‐171555 inhibited in a concentration‐dependent fashion the evoked overflow of DA, an effect antagonized by haloperidol. Stimulation frequencies comparable to normal firing rates of mesocortical neurons (10 Hz) drastically reduced apomorphine‐induced inhibition of DA overflow. Haloperidol produced greater facilitation of DA overflow at 10 than at 1 Hz. Nomifensine, a neuronal uptake inhibitor, enhanced DA overflow. These results indicate that mesocortical DA neurons projecting to the prefrontal cortex have release modulatory autoreceptors of the D2 subtype.