Arecoline via miniosmotic pump improves AF64A-impaired radial maze performance in rats: a possible model of Alzheimer's disease.

Abstract

Male Sprague-Dawley rats, preoperatively trained in a 1-h delay non-match-to-position radial maze task, received bilateral stereotaxic injections of a selective cholinotoxin, ethylcholine aziridinium ion (AF64A: 3 nmol/3 microliters/lateral ventricle). Animals treated with AF64A made significantly more total postdelay errors than vehicle controls. Sustained delivery, via miniosmotic pumps, of arecoline (0.1, 0.3, 1, 3, 10, or 30 mg/kg/day sc for 14 days) attenuated the AF64A-induced cognitive impairment in a dose-dependent manner, producing an inverted U-shaped dose-response function which was optimal at 1.0 mg/kg/day. Following these studies, choline acetyltransferase activity was significantly reduced in hippocampi extracted from the AF64A-treated rats, indicating successful cholinotoxicity. This paradigm may be useful as a possible screen for potential Alzheimer's disease therapeutic agents. This conclusion is supported by published reports of beneficial arecoline effects observed following 2-week intravenous infusions in patients with Alzheimer's disease (Soncrant, Raffaele, Asthana, Berardi, Morris, & Haxby, 1993).

• Authors: A C Bartolomeo, H Morris, C A Boast
• Journal: Neurobiology of learning and memory (Neurobiol Learn Mem) Vol. 68 Issue 3 Pg. 333-42 (Nov 1997) ISSN: 1074-7427 [Print] United States
• PMID: 9398593 (Publication Type: Journal Article)

Chemical References

• Aziridines
• Muscarinic Agonists
• Neurotoxins
• Arecoline
• ethylcholine aziridinium
• Choline

Topics

• Alzheimer Disease (chemically induced, physiopathology)
• Animals
• Arecoline (pharmacology)
• Aziridines (pharmacology)
• Brain (drug effects, physiopathology)
• Brain Mapping
• Cerebral Cortex (drug effects, physiopathology)
• Choline (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hippocampus (drug effects, physiopathology)
• Infusion Pumps, Implantable
• Male
• Maze Learning (drug effects, physiology)
• Mental Recall (drug effects, physiology)
• Muscarinic Agonists (pharmacology)
• Neurotoxins (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Retention, Psychology (drug effects, physiology)