Effect of adenosine A1 receptor antagonist on learning and memory and analysis of its mechanism / 药学学报

ABSTRACT

<p><b>AIM</b>To study the effect of blocking adenosine A1 receptors on learning and memory and the relation with cholinergic and aminoacidergic nerve.</p><p><b>METHODS</b>Using step through test, spectrophotometry and HPLC method, the effect of selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.3, 0.15, 0.075, 0.03, 0.015 microgram, icv) on memory impairment by scopolamine (Scop, 3 mg.kg-1 i.p.) or 2-amino-5-phosphonovaleric (AP5, 2.5 ng, icv), acetylcholinesterase (AChE) activity and aminoacid level in brain of mice was studied.</p><p><b>RESULTS</b>DPCPX was shown to significantly improve scopolamine-induced memory impairment, but not AP5-induced. The activity of AChE in mouse brain was significantly inhibited by large doses of DPCPX in vitro and in vivo test. DPCPX(0.3 microgram, icv) was shown to significantly increase the content of glutamate and aspartic acid in brain of mice. DPCPX (0.3, 0.15 microgram, icv) significantly decrease GABA and increase Glu/GABA in brain of mice.</p><p><b>CONCLUSION</b>The selective adenosine A1 receptor antagonist DPCPX was shown to significantly improve scopolamine but not AP5-induced memory impairment. Large doses of DPCPX was shown to influence the AChE activity and the changes in aminoacid level in brain, especially increase Glu/GABA.</p>