Effects of chronic scopolamine administration on spatial working memory and hippocampal receptors related to learning.
Scopolamine has been used in neuropsychopharmacology as a standard drug that leads to symptoms mimicking cognitive deficits seen during the aging process in healthy humans and animals. Scopolamine is known to be a nonselective muscarinic receptor blocker, but its chronic effect on the expression of certain hippocampal receptors is not clear. The aim of the present study was to determine the effect of chronic scopolamine administration on hippocampal receptor expression and spatial working memory in two different learning tasks, the water maze and the eight-arm radial maze. Male rats (8-12 months) were trained in both tasks. Subsequently, different groups received physiological saline or 0.1, 0.8, or 2 mg/kg scopolamine hydrobromide, respectively, for 15 days. After drug administration, the rats were retested for both tasks, and hippocampal expressions of NR2A, NR2B, nAChRα7, and mAChRM1 receptors were assessed by western blotting analysis. In both tasks, the spatial working memory was decreased dose dependently in all groups compared with the control group. In terms of receptor expressions, 0.8 and 2 mg/kg scopolamine administration significantly decreased NR2A protein expression, which corroborates suggestions of an interaction between cholinergic and glutamatergic receptors in the hippocampus.
Medical Biochemistry Department, Medical Faculty, Suleyman Demirel University, 32040 Cunur/Isparta, Turkey. duygukd@yahoo.com
Duygu K
DK
Doguc
Namik
N
Delibas
Huseyin
H
Vural
Irfan
I
Altuntas
Recep
R
Sutcu
Yonca
Y
Sonmez
D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D012601:Scopolamine / Q000008:administration & dosage / Q000633:toxicity*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D012601:Scopolamine; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; C121001:NR2B NMDA receptor