Int Neurourol J.  2015 Dec;19(4):228-236. 10.5213/inj.2015.19.4.228.

Alpha1-Adrenoceptor Antagonists Improve Memory by Activating N-methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus

• Kim CH
• Ko IG
• Kim SE
• Shin MS
• Kang YH
• Cho JW
• Shin KM
• Kim CJ
• Lim BV
• Kim KH

• KMID: 2380856
• DOI: http://doi.org/10.5213/inj.2015.19.4.228

Abstract

PURPOSE
Alpha1 (alpha1)-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, alpha1-adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an alpha1-adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats.
METHODS
The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate receptors, in hippocampal CA1 neurons.
RESULTS
Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin.
CONCLUSIONS
Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.

Keyword

Tamsulosin; Memory; Apoptosis; Patch-Clamp Techniques; Receptors, N-methyl-D-aspartate

MeSH Terms

Animals
Apoptosis
Blood-Brain Barrier
Brain
Central Nervous System
Dentate Gyrus
Hippocampus*
In Situ Nick-End Labeling
Learning
Lower Urinary Tract Symptoms
Memory*
Memory, Short-Term
N-Methylaspartate
Neurons
Patch-Clamp Techniques
Rats*
Receptors, Ionotropic Glutamate
Receptors, Kainic Acid
Receptors, N-Methyl-D-Aspartate
Urinary Bladder, Overactive
N-Methylaspartate
Receptors, Ionotropic Glutamate
Receptors, Kainic Acid
Receptors, N-Methyl-D-Aspartate