I-stepholidine facilitates inhibition of mPFC DA receptors on subcortical NAc DA release.
OBJECTIVE
To determine whether the D1 agonistic action of (-)-stepholidine (SPD) on the medial prefrontal cortex (mPFC) neuron is involved in the modulation of evoked subcortical dopamine (DA) release from nucleus accumbens (NAc) of rats.


METHODS
With the microinjection of SPD into the mPFC, the ventral 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 mumol.L-1)-evoked DA efflux within the NAc. It indicates that the mPFC DA system is involved in the regulation 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 injection of SPD could not alter the response of DA release by the stimulation of the VTA. Furthermore, the inhibitory effect of SPD on the AMP-evoked DA efflux could be partially reversed by intravenous administration of D1 antagonist Sch-23390 (1 mg.kg-1), but not by D2 antagonist spiperone.


CONCLUSIONS
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.
Zhu
Z T
ZT
Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai 200031, China.
Wu
W R
WR
Fu
Y
Y
Jin
G Z
GZ
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism*; D016627:Oxidopamine; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*
D017447:Receptors, Dopamine D1; D001599:Berberine; C010513:stepholidine; D016627:Oxidopamine; D004298:Dopamine