Effects of stimulation of alpha1-adrenergic and NMDA/glycine-B receptors on learning defects in aged rats

Abstract

The present study was designed to investigate the efficacy of stimulation of alpha₁-adrenoceptors and the strychnine insensitive glycine-B binding sites of the N-methyl-D-aspartate (NMDA) receptor complex to alleviate the age-related defect in water maze (WM) spatial (hidden platform) navigation. We found that daily pretraining IP treatment with 2-(2-chloro-5-trifluoromethylphenylamino) imidazole nitrate (ST 587), an alpha₁-adrenoceptor agonist, at 3000 μg/kg, but not at 1000 μg/kg, facilitated acquisition of water maze spatial navigation in aged rats. However, ST 587 3000 μg/kg (IP) did not stimulate WM spatial reversal learning or cue navigation to a visible platform in aged rats. A partial strychnine insensitive glycine-B binding site agonist, D-cycloserine (DCS) at 10000 μg/kg stimulated acquisition of WM navigation, but had no effect on reversal learning or cue navigation. DCS at 1000 or 3000 μg/kg (IP) had no marked effect on WM spatial navigation, and did not enhance the WM performance improving effect of ST 587 in aged rats. A subthreshold dose of ST 587 1000 μg/kg did not enhance the therapeutic effect of DCS 10000 μg/kg. The present results indicate that activation of alpha₁-adrenoceptors and glycine binding sites of NMDA receptor may to some extent alleviate the age-related defect in spatial navigation. DCS treatment does not enhance the therapeutic effects of ST 587 and vice versa.