5HT Antagonists Attenuate MK801-Impaired Radial Arm Maze Performance in Rats

• Published in: Neurobiology of learning and memory 1999-05, Vol.71 (3), p.259-271
• Main Authors: Boast, Carl, Bartolomeo, Adam C., Morris, Herman, Moyer, John A.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer's disease; Animals; arecoline; Arecoline - therapeutic use; Behavioral psychophysiology; Biological and medical sciences; buspirone; Cognition Disorders - chemically induced; Cognition Disorders - drug therapy; delayed nonmatch-to-sample; dementia; Disease Models, Animal; dizocilpine; Dizocilpine Maleate - adverse effects; Dizocilpine Maleate - metabolism; Drug Synergism; Fundamental and applied biological sciences. Psychology; glutamate; Glutamates - metabolism; Male; Maze Learning - drug effects; Muscarinic Agonists - therapeutic use; Neuroprotective Agents - adverse effects; Neuroprotective Agents - metabolism; Neurotransmission and behavior; ondansetron; Piperazines - therapeutic use; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Pyridines - therapeutic use; Rats; Rats, Sprague-Dawley; ritanserin; Serotonin Antagonists - pharmacology; Serotonin Antagonists - therapeutic use; WAY-100635
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1006/nlme.1998.3886

Glutamatergic hypofunction occurs in Alzheimer's disease (AD). MK801, a noncompetitive blocker of glutamateN-methyl-d-aspartate receptors, was used to disrupt the cognitive performance of rats trained on a delayed nonmatching to sample radial maze task. Drugs which act by blocking serotonin (5-HT) receptors were evaluated for their ability to reduce the cognitive impairment produced by MK801. Specifically, WAY-100635, a selective 5-HT1Areceptor antagonist, buspirone, a 5-HT1Apartial agonist, ritanserin, a 5-HT2antagonist, and ondansetron, a 5-HT3antagonist, were assessed. In addition, the muscarinic agonist arecoline was evaluated for its potential cognitive benefit in this model. It was found that WAY-100635 significantly reduced the cognitive impairment induced by MK801. Treatment with single doses of ritanserin, ondansetron, or arecoline in combination with MK801 did not result in a cognitive impairment, indicating that these drugs attenuated the MK801 impairment. The combination of buspirone and MK801 resulted in an inability of the animals to complete the task. These results suggest that interactions between 5-HT and glutamate may mediate the beneficial effects of reducing cognitive impairment and that 5-HT antagonists, especially selective 5-HT1Aantagonists, may be useful in treating AD. Further, it is indicated that the MK801 model of cognitive impairment may add to the armamentarium of tools available to predict treatment efficacy in AD.