Effect of repeated methamphetamine administration on retrieval of spatial memory and associated activation of MAPK (mitogen-activated protein kinase) in mice

• Main Authors: Chih-leng Liao, 廖芷稜
• Other Authors: Ingrid Y.C. Liu
• Format: Others
• Language: en_US
• Online Access: http://ndltd.ncl.edu.tw/handle/38141860294839083940

碩士 === 慈濟大學 === 神經科學研究所 === 96 === Methamphetamine (METH) is a popular abused drug in Taiwan. It is also a psychositmulant and often used to treat childhood attention deficit hyperactivity disorder (ADHD). Short-term abuse of methamphetamine can cause high wake up, lower fatigue and increase locomotor activity. Long-term abuse of methamphetamine, on the other hand, results in dependence and addiction. Many studies indicated that METH could influence long-term spatial memory, however, results were controversial. It is not clear yet whether METH would enhance or impair spatial memory. In the present study, I investigated the effect of repeated METH administration on performance of long-term spatial memory and its underlying signaling pathway. I used hippocampal-dependent Morris water maze paradigm to study the effect of METH on performance of spatial memory. The mice were administered with METH for 7 consecutive days. Compared with statuses before and after METH injection, my data showed that METH treated groups performed better than saline groups in both hidden platform and probe trial tests. Further, I used Western blotting and immunohistochemistry to demonstrate that enhanced retrieval of spatial memory by repeated METH treatment was through increased phospho-Erk pathway in the hippocampus and cerebellum but independent on p38 pathway. Finally, I used immunofluorescent staining to prove that p-Erk and tyrosine hydroxylase were colocalized in the hippocampus but in not the cerebellum. That is, Erk signaling was activated in dopaminergic neurons of the hippocampus but in other types of cells in the cerebellum.