Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 28; no. 2; pp. 253 - 264
• Main Authors: MISANE, Ilga, ÖBGREN, Sven Ove
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.02.2003; Nature Publishing Group
• Subjects: Alzheimer's disease; Animals; Avoidance Learning - drug effects; Avoidance Learning - physiology; Benzopyrans - pharmacology; Biological and medical sciences; Dementia; Dose-Response Relationship, Drug; Drug Interactions - physiology; Drug toxicity and drugs side effects treatment; Male; Medical sciences; Medicin och hälsovetenskap; Neuropharmacology; Neurosciences; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Piperazines - pharmacology; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - metabolism; Receptors, Serotonin - physiology; Receptors, Serotonin, 5-HT1; Retention; Scopolamine Hydrobromide - pharmacology; Serotonin Antagonists - pharmacology; Serotoninergic system; Toxicity: nervous system and muscle; Sweden; Rat; Toxicity; Esterases; Cognition; acetylcholinesterase inhibitors; Alkaloid; Cholinergic receptor; 5-HT1A Serotonine receptor; Donepezil; Atropine; Subcutaneous administration; Antagonist; 5-HT1A receptors; Tacrine; Hyoscine; Enzyme; Serotonin antagonist; Rodentia; Biological activity; Cholinesterase; Carboxylic ester hydrolases; muscarinic receptors; Vertebrata; passive avoidance; Mammalia; Animal; Hydrolases; Inhibitor; Muscarinic receptor; Avoidance; Parasympatholytic
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1300024

Systemic administration of the muscarinic-receptor antagonists atropine and scopolamine produces cognitive deficits in humans, nonhuman primates and rodents. In humans, these deficits resemble symptoms of dementia seen in Alzheimer's disease. The passive avoidance (PA) task has been one of the most frequently used animal models for studying cholinergic mechanisms in learning and memory. The present study examined the ability of two selective 5-HT(1A) receptor antagonists WAY 100635 and NAD-299 (robalzotan) and two acetylcholinesterase (AChE) inhibitors tacrine and donepezil to attenuate the impairment of PA retention caused by the nonselective muscarinic receptor antagonist scopolamine in the rat. Although demonstrating differences in their temporal kinetics, both WAY 100635 and NAD-299 attenuated the impairment of PA caused by scopolamine (0.3 mg/kg s.c.). Donepezil did not block the PA deficit caused by the 0.3 mg/kg dose of scopolamine, but it prevented the inhibitory effects of the 0.2 mg/kg dose of scopolamine. In contrast, tacrine was effective vs both the 0.2 and 0.3 mg/kg doses of scopolamine. These results indicate that (1). a functional 5-HT(1A) receptor antagonism can attenuate the anterograde amnesia produced by muscarinic-receptor blockade, and (2). the AChE inhibitors tacrine and donepezil differ in their ability to modify muscarinic-receptor-mediated function in vivo. These results suggest that 5-HT(1A) receptor antagonists may have a potential in the treatment of cognitive symptoms in psychopathologies characterized by reduced ACh transmission such as Alzheimer's disease.