Effect of adenosine A₁ receptor antagonist on learning and memory and analysis of its mechanism

AimTo study the effect of blocking adenosine A₁ receptors on learning and memory and the relation with cholinergic and aminoacidergic nerve. Methods Using step through test, spectrophotometry and HPLC mothod, the effect of selective adenosine A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.3, 0.15, 0.075, 0.03, 0.015 μg, icv) on memory impairment by scopolamine(Scop, 3 mg·kg^-1 ip) or 2-amino-5-phosphonovaleric(AP₅, 2.5 ng, icv), acetylcholinesterase(AChE) activity and aminoacid level in brain of mice was studied. Results 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 andin vivo test. DPCPX(0.3 μg, icv) was shown to significantly increase the content of glutamate and aspartic acid in brain of mice. DPCPX (0.3, 0.15μg, icv) significantly decrease GABA and increase Glu/GABA in brain of mice. Conclusion 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.