Alpha1-Adrenergic Antagonist Can Influence Memory Function? Effect of Alpha1-Adrenergic Antagonist, Tamsulosin, on Activation of NMDA Receptor in Hippocampus of Rats

다국어 초록 (Multilingual Abstract)

Alpha1 (α1)-adrenoceptor antagonists have widely been used for the treatment of overactive bladder (OAB) syndrome. OAB is characterized by urgency usually with frequency and nocturia. Treatment drugs act on peripheral tissues and on the central nervous system, because of their ability to readily cross the blood-brain barrier. It has been suggested that α1-adrenoceptor antagonists enhance brain function. In the present study, we investigated the effect of tamsulosin, an α1-adrenoceptor antagonist, on short-term memory and spatial learning ability in rats.
The step-down avoidance test for short-term memory and radial 8-arm maze test for spatial learning ability were conducted. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to evaluate the effect of tamsulosin on the level of apoptosis in the hippocampal dentate gyrus. Patch clamp recording was used to evaluate the effects of tamsulosin on the ionotropic glutamate receptor-mediated ion currents, such as N-methyl-D-aspartate (NMDA) receptor-, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-, and kainate (KA) receptor-mediated ion currents, in the hippocampal CA1 neurons.
The present results showed that tamsulosin treatment improved short-term memory and spatial learning ability without alteration of the level of apoptosis. The amplitude of NMDA-induced ion current was significantly increased by tamsulosin application in a dose-dependent manner. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin application.
The present study showed that tamsulosin might enhance memory functions through activation of NMDA receptor-mediated ion current in the hippocampus.

목차 (Table of Contents)

• 국문초록 ----------------------------------------------1
• 그림목차---------------------------------------------- 4
• 머 리 말 ---------------------------------------------- 5
• 방 법 ----------------------------------------------- 9
• 결 과 -----------------------------------------------18
• 고 찰 -----------------------------------------------29
• 참고문헌 ----------------------------------------------34
• 영어인준서 --------------------------------------------41
• 영문초록 ----------------------------------------------42