Nicotine promotes the utility of short-term memory during visual search in macaque monkeys. 2022

Ryo Sawagashira, and Masaki Tanaka
Department of Physiology, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan. rsawa6133@med.hokudai.ac.jp.

BACKGROUND The central cholinergic system is a major therapeutic target for restoring cognitive functions. Although manipulation of cholinergic signaling is known to alter working memory (WM), the underlying mechanism remains unclear. It is widely accepted that WM consists of multiple functional modules, one storing short-term memory and the other manipulating and utilizing it. A recently developed visual search task and a relevant model can be used to assess multiple components of WM during administration of acetylcholine receptor (AChR)-related substances. OBJECTIVE The effects of systemic administration of AChR-related agents on WM and eye movements were examined during the oculomotor foraging task. METHODS Three monkeys performing the task received an intramuscular injection of saline or the following AChR-related agents: nicotine (24 or 56 μg/kg), mecamylamine (nicotinic AChR antagonist, 1.0 mg/kg), oxotremorine (muscarinic AChR agonist, 3.0 µg/kg), and scopolamine (muscarinic AChR antagonist, 20 μg/kg). The task was to find a target among 15 identical objects by making eye movements within 6 s. The data were analyzed according to the foraging model that incorporated three parameters. RESULTS Nicotine and mecamylamine significantly increased the utility but not the capacity of short-term memory, while muscarinic AChR-related agents did not alter any WM parameters. Further regression analyses with a mixed-effect model showed that the beneficial effect of nicotine on memory utility remained after considering eye movement variability, but the beneficial effect of mecamylamine disappeared. CONCLUSIONS Nicotine improves visual search, mainly by increasing the utility of short-term memory, with minimal changes in oculomotor parameters.

UI MeSH Term Description Entries
D008251 Macaca A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes. Ape, Barbary,Ape, Black,Ape, Celebes,Barbary Ape,Black Ape,Celebes Ape,Macaque,Apes, Barbary,Apes, Black,Apes, Celebes,Barbary Apes,Black Apes,Celebes Apes,Macacas,Macaques
D008464 Mecamylamine A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.
D008570 Memory, Short-Term Remembrance of information for a few seconds to hours. Immediate Recall,Memory, Immediate,Working Memory,Memory, Shortterm,Immediate Memories,Immediate Memory,Immediate Recalls,Memories, Immediate,Memories, Short-Term,Memories, Shortterm,Memory, Short Term,Recall, Immediate,Recalls, Immediate,Short-Term Memories,Short-Term Memory,Shortterm Memories,Shortterm Memory,Working Memories
D009538 Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Nicotine Bitartrate,Nicotine Tartrate
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000882 Haplorhini A suborder of PRIMATES consisting of six families: CEBIDAE (some New World monkeys), ATELIDAE (some New World monkeys), CERCOPITHECIDAE (Old World monkeys), HYLOBATIDAE (gibbons and siamangs), CALLITRICHINAE (marmosets and tamarins), and HOMINIDAE (humans and great apes). Anthropoidea,Monkeys,Anthropoids,Monkey
D018727 Muscarinic Antagonists Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. Antimuscarinic,Antimuscarinic Agent,Antimuscarinic Agents,Cholinergic Muscarinic Antagonist,Muscarinic Antagonist,Antimuscarinics,Cholinergic Muscarinic Antagonists,Agent, Antimuscarinic,Agents, Antimuscarinic,Antagonist, Cholinergic Muscarinic,Antagonist, Muscarinic,Antagonists, Cholinergic Muscarinic,Antagonists, Muscarinic,Muscarinic Antagonist, Cholinergic,Muscarinic Antagonists, Cholinergic
D018733 Nicotinic Antagonists Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses. Antagonists, Nicotinic

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