Effects And Mechanisms Of Acute Methamphetamine Use On The Gamma Network Oscillations In Rat Hippocampal CA3 Area

BackgroundNeural network oscillation is rhythmic,synchronized neural activity existing in multiple regions,such as cerebral cortex,hippocampus and the amygdala,and closely related to the to the higher brain function such as leaning and memory.It has been reported acute methamphetamine?MA?exposure increased gamma oscillation,but the cellular mechanism is not clear.ObjectivesThis study attempts to examine the effects of MA on the neural network oscillation.and the cellular signaling pathyway involved.The constant temperature?28?³2??interface perfusion system containing gas Methods1.mixture?95%O₂+5%CO₂?and artificial cerebrospinal fluid?ACSF?perfusion?flow rate:1.5 ml/min,pH:7.35⁷.45?.2.SD rats?3-4 weeks?were anaesthetized and perfused with chilled?4-5°C?ACSF until limbs turned white.3.The brain was removed quickly and the horizontal hippocampal slices?400?m?were cut using LEICA VT 1000S vibrating slicer.4.Slices were transferred to an interface recording chamber,with ACSF?28?³2?,3-4ml/min?containing the mixed gas,the slices were allowed to equilibrate in this medium for 1h prior to recording.Gamma?30⁸0 Hz?oscillations were induced by bath application of kainate.5.The effects of MA?20?M?on gamma oscillations and the effects of DA receptor antagonists,NMDA receptor antagonists and PI3K,Akt,ERK,PKA inhibitors on the role of MA were tested.Data were analyzed by Spike 2 software.Statistical tests were performed using SigmaStat software.Experimental data are expressed as mean±standard error of mean.Measures were considered statistically significant if P?0.05.Results1.MA increased gamma oscillations on hippocampal.2.Wortmannin?0.2?M?did not block the role of MA on gamma.3.U0126?2.5?M?and H89?10?M?had no role on MA enhancement of gamma.4.Raclopride,SCH23390 and D-AP5 at 10?M block the effect of MA.5.TCBN?5?M?itself increased gamma oscillations,but blocked the effect of MA.ConclusionsMA significantly increased gamma power,which is associated with the activation of D2R,NMDAR and Akt signaling moleculaes.