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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.

With microinjection of 6-hydroxydopamine (6-OHDA) into the ventral hippocampus (VHIP) of rats, the effect of 6-OHDA lesion of hippocampal noradrenergic system on the plasma corticosterone (CS) response to acute hypoxia was investigated. It was found that the plasma CS response to inhalation of 10.4% O2 (30 min) was increased markedly; while the plasma CS level and the noradrenaline (NA) contents in hippocampus were decreased (-33.2% and -38.5%, respectively) 2 weeks after microinfusion of 6-OHDA (8 micrograms/2 microliters) into VHIP; however, the CS response to acute hypoxia was unaffected by 6-OHDA lesion of VHIP. The results above suggest that NA in hippocampus may participate in the regulation of the hypoxia-induced increase of plasma CS concentration in rats.

Experimens were performed on 36 cats, showing that stimulation of the central end of the left major splanchnic nerve induced an increase of the plasma cortisol level. The centripetal effect was abolished by lesioning the septal nuclei, just as the same as injection of propranolol into the nuclei; but phentolamine had no such preventive action. All the findings show that it is the noradrenergic beta-receptor system of the septal nuclei that exerts a considerable effect on cortisol secretion.