Ocotillol F <sub> 11 </ Sub> Antagonist Of Methamphetamine Neurotoxicity Study

PF₁₁ did not infuence the conditioned place preference per se, yet markedly blocked the conditioned place preference to MA.PF₁₁ did not infuence locomotor activity per se,yet inhibited the increasing of MA-induced locomotor activity.Those results suggest that PF₁₁ significantly antagonized psychic dependence of MA.Then,we had studied that the effect of PF₁₁ on MA(2.5,5.0mg/kg)-induced DA,5-HT and their metabolites changes in hypothalamus, hippocampus, striatum,cerebal cortex of rat by using HPLC-ECD.The results showed that PF₁₁ didn't influence the contents of DA,5-HT and their metabolites levels in different brain regions.But PFn(5.6mg/kg) significantly antagonized increasing DA in MA (2.5mg/kg,i.p) -treated rat in the hippocampus .The behaviour tests suggested that locomotor activities and anxious behaviour didn't significantly change in MA-dependent mice with natural withdrawal syndrome.But using HPLC-ECD,PF₁₁ inhibited the decrease of dopamine contents in brain instead of in striatum in MA-dependent mices with natural withdrawal.In addition,PF₁₁ significantly antagonized the development of the reverse tolerance,as shown by increase in locomotor activity to MA.This article studied the protect effect of PFu on MA(4X 10mg/kg)-induced neurotoxicity in light/dark task, PF₁₁ did not significantly influence on anxietybehaviour but greatly decreased time spent in dark box in MA-induced neurotoxicity mices. T-maze,compared with the control,The latency time had been prolonged in MA-induced neurotoxity mices.PF₁₁ greatly shorted the longed latency time .By using Morris Maze task,The results indicated the learning and memory impairment was continuously maintained by MA-induced neurotoxity,PF₁₁ significantly antagonized the learning and memory impairment by MA-induced neurotoxicity, Motor incoordination was studied by using the rotating rod method in mice,PF₁₁ markedly alleviated the injury induced by MA.using HPLC-ECD,there were markedly decrease the contents of DA,DOPAC,HVA and 5-HIAA,PF₁₁ markedly antagonised decrease of DA in MA-induced neurotoxicity.En conclusion, PFn may be directly or indirectly mediate DA system and markedly anagonist MA pharmacological activities. Those finding suggest a potential therapeutic role of PFn in the combat against MA-relate ailments.