Effects of different doses of methamphetamine on spatial learning and memory in mice and the mechanism / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the different-dose effects of methamphetamine (METH) on spatial learning and memory and the possible mechanisms. Methods: C57BL/6 mice were treated with 0.5, 1.0 and 2.0 mg/kg of METH or normal saline. The drug was injected intraperitoneally 30 min prior to the Morris water maze. All mice experienced 5 consecutive days' positioning navigation experiment and the spatial exploration experiment conducted 24 hours after the last training trial. Immediately after the probe test, the mice were killed by cervical dislocation and the hippocampus was dissected. Western blot was used to detect changes in phosphorylation levels of extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) in the hippocampus. Results: Compared with the mice in saline group, those in 1.0 mg/kg METH group had a significantly shorter latency (P<0.05), spent more time in the target quadrant (P<0.05), and had more platform site crossings (P<0.05). Moreover, 0.5 and 2.0 mg/kg of METH did not significantly affect the mice's spatial learning and memory, but 0.5 mg/kg of METH showed a memory-promoting trend, while 2.0 mg/kg of METH showed a memory-destroying trend. METH of 1.0 mg/kg significantly increased p-ERK1/2 (P<0.05) and p-CREB (P<0.05) levels in the hippocampus. Conclusion: METH of 1.0 mg/kg significantly improved mice's spatial learning and memory. The effect of METH is an inverted U-curve among three doses of METH at 0.5, 1.0 and 2.0 mg/kg. ERK1/2 and CREB in the hippocampus may be involved in METH-induced improvement of spatial learning and memory in mice.