Electrophysiological study on biphasic firing activity elicited by D1 agonistic-D2 antagonistic action of (-)-stepholidine in nucleus accumbens
10.3321/j.issn:0371-0874.2000.02.008
- VernacularTitle:左旋千金藤啶碱D1激动-D2阻滞作用引起伏核双相放电活动的电生理研究
- Author:
Zi-Tao ZHU
1
;
Yu FU
;
Guo-Yuan HU
;
Guo-Zhang JIN
Author Information
1. 中国科学院上海药物研究所
- Keywords:
(-)-stepholidine;
dopamine receptors;
nucleus accumbens;
electrophysiology;
6-hydroxydopamine lesion
- From:
Acta Physiologica Sinica
2000;52(2):123-130
- CountryChina
- Language:Chinese
-
Abstract:
Our previous work has demonstrated that (-)-stepholidine (SPD) has dual action, ie D1 agonistic-D2 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 D2 antagonist spiperone, SPD only exerted an increasing effect, which was subsequently reversed by the D1 antagonist SCH-23390. Moreover, SCH-23390 could prevent the rate of increase elicited by SPD at high doses, presumably due to the D1 agonistic action of SPD on the activity of NAc neuron. On the other hand, the inhibition of NAc firing elicited by either D2 agonist LY171555 or D1/D2 agonists apomorphine was completely reversed by SPD, suggesting an antagonistic action of SPD to D2 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 D1 agonistic-D2 antagonistic dual action on NAc neuron activity, which may be beneficial to the treatment of schizophrenia.
