These preceding reports recommend that memor.
These ndings recommend (-)-MK 801 Maleate that the antagonism shown by tanshinone I against diazepaminduced memory decits might not be directly derived from GABAA receptor blockade. We hypothesized that the memoryameliorating effect of tanshinone I against diazepam is not due to antagonism at GABAA receptors, but rather to the sharing or convergence of an intracellular signalling pathway, such as the ERK?CREB signalling pathway. In a pilot study, we found that tanshinone I and other tanshinone congeners, namely, tanshinone I, tanshinone IIA, cryptotanshinone and 15,16 dihydrotanshinone I, increased ERK phosphorylation within 1 h in normal mice. Here, we investigated the mode of action of tanshinone I with respect to ERK?CREB phosphorylation, and sought to determine whether tanshinone I treatment affects memory.
Passive avoidance performance was carried out in two identical light and dark square boxes separated by a NSCLC guillotine door, as described in our previous report. The illuminated compartment contained a 50 W bulb, and its oor was composed of 2 mm stainless steel rods spaced with centres 1 cm apart. A mouse was initially placed in the illuminated compartment for the acquisition trial, and the door between the two compartments was opened 10 s later. When the mouse entered the dark compartment, the guillotine door was automatically closed and an electrical foot shock of 3 s duration was delivered through the stainless steel rods. The mice were given tanshinone I 40 min before the acquisition trial. Memory impairment was induced by diazepam, a selective antagonist of the benzodiazepine site of the GABAA receptor or MK 801, an NMDA receptor channel blocker, which was administered 10 min after tanshinone I or vehicle.
The effect of U0126 on memory impairment in the passive avoidance task was also investigated. Our pilot studies conrmed that the effective dose that could induce memory impairment was over 1 nmol.
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