Ameliorative effects of the centrally active cholinesterase inhibitor, NIK-247, on impairment of working memory in rats

• Published in: Physiology & behavior Vol. 53; no. 1; pp. 5 - 10
• Main Authors: Yamamoto, Tsuneyuki, Ohno, Masuo, Kitajima, Iwao, Yatsugi, Shin-Ichi, Ueki, Showa
• Format: Journal Article
• Language: English
• Published: Cambridge Elsevier Inc 1993; New York, NY Elsevier
• Subjects: Acetylcholinesterase - physiology; Aminoquinolines - pharmacology; Animals; Appetitive Behavior - drug effects; Appetitive Behavior - physiology; Behavioral psychophysiology; Biological and medical sciences; Brain - blood supply; Brain - drug effects; Brain - physiology; Cerebral ischemia; Cholinergic system; Cholinesterase Inhibitors; Fundamental and applied biological sciences. Psychology; Hippocampal lesion; Hippocampus - drug effects; Hippocampus - physiology; Male; Mental Recall - drug effects; Mental Recall - physiology; Neurotransmission and behavior; NIK-247; Orientation - drug effects; Orientation - physiology; Physostigmine; Physostigmine - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychotropic Drugs - pharmacology; Rats; Rats, Wistar; Receptors, Cholinergic - drug effects; Receptors, Cholinergic - physiology; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Retention (Psychology) - drug effects; Retention (Psychology) - physiology; Runway task; Scopolamine; Scopolamine - pharmacology; Tacrine - pharmacology; Tetrahydroaminoacridine (THA); Working memory; Cerebral ischemia; Scopolamine; Tetrahydroaminoacridine (THA); Runway task; NIK-247; Physostigmine; Cholinergic system; Hippocampal lesion; Working memory; Animal model; Intraperitoneal administration; Rat; Enzyme; Rodentia; Central nervous system; Cholinesterase; Vertebrata; Mammalia; Acquisition process; Ischemia; Animal; Inhibitor; Lesion; Deafferentation; Hippocampus; Brain (vertebrata)
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/0031-9384(93)90003-X

Using a three-panel runway task, the effects of NIK-247 on impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia were investigated in rats; these effects were compared with those of the well-known cholinesterase inhibitors, tetrahydroaminoacridine (THA) and physostigmine. Intraperitoneal injection of scopolamine (0.56 mg/kg) significantly increased the number of errors (pushes made on the two incorrect panels of the three-panel gates located at four choice points). NIK-247 (3.2–18 mg/kg PO), THA (1–10 mg/kg PO), and physostigmine (0.1 and 0.32 mg/kg IP) dose-dependently reduced the increase in errors induced by scopolamine. NIK-247 (32 mg/kg) was also effective in reducing the increase in errors produced by lesions of the dorsal hippocampus. A 5-min period of cerebral ischemia markedly increased the number of errors. NIK-247 (3.2 and 10 mg/kg), given immediately after blood flow recirculation and again 20 min before the runway test carried out 24 h after ischemia, significantly reduced the increase in errors expected to occur after ischemia. Tetrahydroaminoacridine (3.2 mg/kg) and physostigmine (0.1 mg/kg) similarly reversed the increased errors in ischemic rats. These results suggest that NIK-247 alleviates the impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia, possibly through activation of the central cholinergic system.