Modulation of medical prefrontal cortical D1 receptors on the excitatory firing activity of nucleus accumbens neurons elicited by (-)-Stepholidine.

(-)-Stepholidine (SPD), with D1 agonistic action, elicited an excitatory firing activity of nucleus accumbens (NAc) neurons by intravenous administration, but this effect was hardly observed by iontophoresis of SPD into the NAc. The present study intends to determine whether D1 receptors in the medial prefrontal cortex (mPFC) are involved in the action of SPD on the firing activity of NAc neurons in the chloral hydrate-anesthetized male rats. The results showed that the intra-mPFC microinjected SCH-23390 (D1 antagonist, 30 mM), but not the D2 antagonist spiperone (30 mM), significantly attenuated the enhanced firing activity induced by intravenous injection of SPD (2 mg/kg). Similarly, the excitatory firing of NAc neurons was also exhibited by the microinjection of either SPD or D1 agonist SKF-38393 into the mPFC. The SPD-induced excitatory effect was in a dose-dependent way from 277.8 +/- 51.3% (10 mM) to 1105.4 +/- 283.5% (30 mM) of NAc basal firing, which was completely reversed by SCH-23390 (i.v.). Furthermore, the direct D1 agonistic action of SPD on the mPFC neuron was observed with microiontophoresis. These results indicate that SPD possesses a direct agonistic action on the mPFC D1 receptors, by which it modulates the firing activity of NAc neurons.