Coompo Research Chemicals

In the one-trial step-down and step-through passive avoidance tests, although pseudoginsenoside-F11 used alone did not affect passive avoidance behaviour in naive mice, the latency of avoidance shortened by intraperitoneal scopolamine (2 mg kg-1) was prolonged after intragastric administration of pseudoginsenoside-F11 (2 or 4 mg kg−1 for five days) in both test systems in mice. In the water-maze test, in mice, the time taken to locate the platform after administration of pseudoginsenoside-F11 was shorter than that after administration of scopolamine (1 mg kg−1 i.p.). In the two-way active avoidance response test, the latency of avoidance was significantly shorter for the pseudoginsenoside-F11-(1 • 2or 2 • 4 mg kg−1 i.g. for five days) and scopolamine-treated group than for the group of rats given scopolamine only (2 mg kg−1, i.p.). The percentage avoidance was also reduced after intraperitoneal injection of scopolamine, but was reversed by administration of pseudo-ginsenoside-F11. These results suggest that pseudoginsenoside-F11 antagonized the memory dysfunction induced by scopolamine. However, the mechanism of the memory facilitative action of pseudoginsenoside-F11 merits further elucidation.

Pseudoginsenoside-F11 (PF11) has been shown to antagonize the behavioral actions of morphine. Biochemical experiments revealed that PF11 could inhibit diprenorphine (DIP) binding with an IC50 of ∼6.1 μM and reduced the binding potency of morphine in Chinese hamster ovary (CHO)-μ cells. Furthermore, PF11 significantly attenuated morphine-stimulated [35S]GTPγS binding in a dose dependent manner, and strongly decreased the efficacy of morphine to inhibit intracellular cAMP production. In addition, PF11 pretreatment could also significantly inhibit naloxone induced cAMP overshoot in the morphine-pretreated cells. However, PF11per se had no effect on either [35S]GTPγS binding or intracellular cAMP accumulation. These data suggested that PF11 antagonized the morphine stimulated opioid receptor signalling directly at the cellular level.

To further investigate the effects of PF11 on morphine abuse and the underlying mechanisms, we tested the effects of PF11 on morphine-induced development of behavioral sensitization and alterations in glutamate levels in the medial prefrontal cortex (mPFC) in freely moving mice by using in vivo microdialysis. As the results shown, PF11 antagonized the development of behavioral sensitization and decrease of glutamate in the mPFC induced by morphine. Therefore, these findings suggest that PF11 may block the development of morphine-induced behavioral sensitization via its effect, at least partially, on the glutamatergic system in the mPFC.