title: Attenuation in rats of impairments of memory by scopolamine, a muscarinic receptor antagonist, by mecamylamine, a nicotinic receptor antagonist.
abstract: BACKGROUND
  Scopolamine, a muscarinic antagonist, impairs learning and memory for many tasks, supporting an important role for the cholinergic system in these cognitive functions. The findings are most often interpreted to indicate that a decrease in postsynaptic muscarinic receptor activation mediates the memory impairments. However, scopolamine also results in increased release of acetylcholine in the brain as a result of blocking presynaptic muscarinic receptors.
  
  
  OBJECTIVE
  The present experiments assess whether scopolamine-induced increases in acetylcholine release may impair memory by overstimulating postsynaptic cholinergic nicotinic receptors, i.e., by reaching the high end of a nicotinic receptor activation inverted-U dose-response function.
  
  
  RESULTS
  Rats tested in a spontaneous alternation task showed dose-dependent working memory deficits with systemic injections of mecamylamine and scopolamine. When an amnestic dose of scopolamine (0.15 mg/kg) was co-administered with a subamnestic dose of mecamylamine (0.25 mg/kg), this dose of mecamylamine significantly attenuated the scopolamine-induced memory impairments. We next assessed the levels of acetylcholine release in the hippocampus in the presence of scopolamine and mecamylamine. Mecamylamine injections resulted in decreased release of acetylcholine, while scopolamine administration caused a large increase in acetylcholine release.
  
  
  CONCLUSIONS
  These findings indicate that a nicotinic antagonist can attenuate impairments in memory produced by a muscarinic antagonist. The nicotinic antagonist may block excessive activation of nicotinic receptors postsynaptically or attenuate increases in acetylcholine release presynaptically. Either effect of a nicotinic antagonist-to decrease scopolamine-induced increases in acetylcholine output or to decrease postsynaptic acetylcholine receptor activation-may mediate the negative effects on memory of muscarinic antagonists.
authors.affiliation: Department of Biology, Syracuse University, 114 Life Sciences Complex, Syracuse, NY, 13244, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Newman
authors.affiliation: Department of Biology, Syracuse University, 114 Life Sciences Complex, Syracuse, NY, 13244, USA. pegold@syr.edu.
authors.forename: P E
authors.initials: PE
authors.lastname: Gold
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000627:therapeutic use*; D008569:Memory Disorders / Q000188:drug therapy* / Q000517:prevention & control*; D008570:Memory, Short-Term / Q000187:drug effects; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D012601:Scopolamine; D000109:Acetylcholine
keywords: Aging; Alzheimer; Autoreceptor; Cholinergic; Cholinesterase inhibitor; Hippocampus; In vivo microdialysis; Muscarinic; Nicotinic; Spatial working memory