l-stepholidine facilitates inhibition of mPFC DA receptors on subcortical NAc DA release

AIM: To determine whether the D-1 agonistic action of (-)-stepholidine (SPD ) on the medial prefrontal cortex (mPFC) neuron is involved in the modulati on of evoked subcortical dopamine (DA) release from nucleus accumbens (NAc) of rats. METHODS: With the microinjection of SPD into the mPFC, the ventra l tegmental area (VTA)-stimulated or amphetamine (AMP)-evoked DA efflux in the NAc was detected by microdialysis + HPLC-ECD in the 6-hydroxydopamine ( 6-OHDA)-lesioned and intact rats. RESULTS: The depletion of DA in the mPFC did not modify both the basal level and the VTA-stimulated DA efflux in the NAc, but significantly facilitated the AMP (20 mu mol.L-1)-evoked DA efflu x within the NAc. It indicates that the mPFC DA system is involved in the r egulation of evoked DA release in the NAc. Besides, the AMP-evoked increase of the extracellular DA release in the NAc was significantly attenuated by SPD (10, 30 mmol . L-1) microinjection into the mPFC, though this injectio n of SPD could not alter the response of DA release by the stimulation of t he VTA. Furthermore, the inhibitory effect of SPD on the AMP-evoked DA effl ux could be partially reversed by intravenous administration of D-1 antagon ist Sch-23390 (1 mg . kg(-1)), but not by D-2 antagonist spiperone. CONCLUS ION: SPD is capable of enhancing the function of D1 receptors in the mPFC, by which it facilitates the inhibition of DA release in the NAc.