Electrophysiological study on biphasic firing activity elicited by D(1) agonistic-D(2) antagonistic action of (-)-stepholidine in nucleus accumbens.
Our previous work has demonstrated that (-)-stepholidine (SPD) has dual action, ie D(1) agonistic-D(2) antagonistic action on DA receptors in the nigra-striatal dopamine (DA) system. The present study attempted to ascertain its dual action on the mesolimbic DA system. The firing activities of the nucleus accumbens (NAc) neurons were extracellularly recorded with intravenous and iontophoretic administration of the drug in 6-hydroxydopamine (6-OHDA)-lesioned and intact rats. The results showed that SPD produced a consistently biphasic firing of NAc neurons during the cumulative doses of 0.02  2 mg/kg, iv. When the rats were pretreated with D(2) antagonist spiperone, SPD only exerted an increasing effect, which was subsequently reversed by the D(1) antagonist SCH-23390. Moreover, SCH-23390 could prevent the rate of increase elicited by SPD at high doses, presumably due to the D(1) agonistic action of SPD on the activity of NAc neuron. On the other hand, the inhibition of NAc firing elicited by either D(2) agonist LY171555 or D(1)/D(2) agonists apomorphine was completely reversed by SPD, suggesting an antagonistic action of SPD to D(2) receptors. In 6-OHDA-lesioned rats, iontophoresis of SPD also had an inhibitory effect in the majority of NAc neurons (91%) as SKF-38393 did. This inhibition could be completely blocked by the ejection of SCH-23390, but not by spiperone. These results indicate that SPD also has a D(1) agonistic-D(2) antagonistic dual action on NAc neuron activity, which may be beneficial to the treatment of schizophrenia.
Zhu
Z T
ZT
Department of Pharmacology of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.
Fu
Y
Y
Hu
G Y
GY
Jin
G Z
GZ
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*
D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D001599:Berberine; C010513:stepholidine; D016627:Oxidopamine