Effects of stimulation of alpha 1-adrenergic and NMDA/glycine-B receptors on learning defects in aged rats.
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 micrograms/kg, but not at 1000 micrograms/kg, facilitated acquisition of water maze spatial navigation in aged rats. However, ST 587 3000 micrograms/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 micrograms/kg stimulated acquisition of WM navigation, but had no effect on reversal learning or cue navigation. DCS at 1000 or 3000 micrograms/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 micrograms/kg did not enhance the therapeutic effect of DCS 1000 micrograms/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.
Riekkinen
M
M
Department of Neuroscience and Neurology, University of Kuopio, Finland.
Kemppainen
S
S
Riekkinen
P
P
D000375:Aging / Q000187:drug effects*; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003523:Cycloserine / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018009:Receptors, Glycine / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D018340:Receptors, Adrenergic, alpha-1; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C030655:St 587; D003523:Cycloserine; D003000:Clonidine