D-cycloserine attenuates scopolamine-induced learning and memory deficits in rats.
The muscarinic antagonist scopolamine (SCOP; 1.0 mg/kg, ip) impaired both the acquisition of a learning task in the Morris water maze (MWM) and choice accuracy in the T-maze reinforced alternation procedure in rats. Acetylcholinesterase inhibitors (AChEIs) have been shown to attenuate these deficits. D-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex, was investigated for its effects on SCOP-induced dementia in the MWM and T-maze paradigms. Combined administration of SCOP and DCS (3.0, 10.0, or 30.0 mg/kg, ip; 30 min pretreat) significantly reversed SCOP-induced deficits in the T-maze as measured by percentage correct choices. In addition, DCS (3.0 or 10.0 mg/kg, ip) significantly attenuated SCOP-induced deficits in the MWM as measured by latency to find the submerged platform. For comparison, the long-acting acetylcholinesterase inhibitor galanthamine (GAL) was tested in the T-maze (1.25, 2.5, or 5.0 mg/kg, ip) and the MWM (2.5 or 5.0 mg/kg, ip). GAL attenuated SCOP-induced deficits in both learning and memory models similar to DCS. These data suggest that the strychnine-insensitive partial glycine agonist, D-cycloserine, may be efficacious in disease states of central cholinergic hypofunction such as Alzheimer's disease.
Fishkin
R J
RJ
Hoechst-Roussel Pharmaceuticals, Inc., Somerville, New Jersey 08876-1258.
Ince
E S
ES
Carlezon
W A
WA
Dunn
R W
RW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003523:Cycloserine / Q000493:pharmacokinetics*; D003704:Dementia / Q000139:chemically induced / Q000378:metabolism; D005702:Galantamine / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D007859:Learning Disabilities / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012602:Scopolamine Derivatives / Q000378:metabolism / Q000494:pharmacology*; D013028:Space Perception / Q000187:drug effects
D012602:Scopolamine Derivatives; D005702:Galantamine; D003523:Cycloserine