Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion

Ruotsalainen, Sirja; Miettinen, Raija; Macdonald, Ewan; Koivisto, Esa; Sirviö, Jouni

doi:10.1007/s002130050032

Cited by 47 publications

(27 citation statements)

References 45 publications

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“…Behavioral studies with experimental animals demonstrated that some neurotoxin lesions of the basal forebrain-cortical cholinergic system induced profound deficits of attentional processes in a five-choice serial reaction time task, and scopolamine, a muscarinic receptor antagonist, but not mecamylamine, a nicotinic receptor antagonist, impaired attentional processes. 9,[17][18][19][20] Thus these facts suggest that the cholinergic system, especially muscarinic receptors, may be essential for attention and arousal. The low dose (0.3 mg/kg) of methamphetamine significantly shortened the CRT, in agreement with the findings of a previous study.…”

Section: Discussionmentioning

confidence: 97%

“…NR is generally disregarded in the visual discrimination task, although omissions are used in some tasks, because a CR is calculated not by dividing the number of CR trials by the number of total trials, but by dividing it by the total number of response trials. 7,8,17,18) In the present study, we calculated each response rate by dividing the number of each four response trials by the number of total trials, that is, 30 trials. Therefore the present method had advantages allowing the influence of various drugs and experimental treatments on the performance of a two-lever CRT task to be evaluated by measuring NR and DRO response with activity during 30 trials.…”

Section: Discussionmentioning

confidence: 99%

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The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

Mishima

Fujii

Aoo

et al. 2002

Biological & Pharmaceutical Bulletin

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Information processes through the learning and memory system consist of three steps: attention (arousal, decisionmaking, motivation, etc.); short-term memory (working memory); and long-term memory (reference memory).1) Attention is used in experimental and human clinical studies to mean the ability to perceive or focus on certain stimuli, but to ignore others in the environment. When people and animals are confronted with a stimulus in the environment, they must usually decide whether they need to remember it and they memorize it as a part of two memory systems (short-term memory and long-term memory) through attentional processes if necessary. Thus most investigators have found that this mechanism plays an important role in information processing and memory processing.A choice reaction time (CRT) task has been regarded as a good measure in experimental and human clinical studies on cognitive performance capability (attention, arousal, decision-making, motivation, etc.), especially visual attention. 2-4)The pioneering work of the group of Robbins in attentional processes using a five-choice serial reaction time task has shown that cholinergic innervation of the forebrain is important in attentional processes, noradrenergic innervation permits accurate performance during arousing situations, dopaminergic innervation of the nucleus accumbens is involved in behavioral activation, and forebrain serotonin (5-HT) is involved in the control of impulsive behavior. [5][6][7][8][9][10] We also reported that ischemic-hypoxic insult to neonatal rats and methamphetamine produced severe impairment of attention in a two-lever correct response (CR) task.11,12) Although a variety of neurons and neurotransmitters have thus been implicated in attentional processes in the five-choice serial reaction time task, the pharmacological characterization in the attentional processes of a two lever CRT task is not understood well. The objective of the present study was to investigate the pharmacological characterization in the attentional processes of a two-lever CRT task using 10 different centrally acting drugs: scopolamine, a nonselective muscarinic receptor antagonist; methamphetamine, a psychostimulant; D 9 -tetrahydrocannabinol (THC), the major psychoactive component of marijuana; prazosin, a noradrenergic a 1 receptor antagonist; 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT), a selective 5-HT 1A receptor agonist; muscimol, a GABA A receptor agonist; dizocilpine (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist; 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride (YM90K), an alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor antagonist; N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor; and nilvadipine, an L-type Ca 2ϩ channel blocker. MATERIALS AND METHODS AnimalsMale Wistar rats weighing 200-250 g were obtained from the Kyu-Do Co., Ltd. (Saga, Japan), and were housed in groups of 4 to 5 per cage, in a room with a controlled temperature of 23Ϯ2°...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

Mishima

Fujii

Aoo

et al. 2002

Biological & Pharmaceutical Bulletin

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“…Although there is a large body of research investigating the PCA-induced impairments, most of these studies examined behavioral changes immediately after PCA administration (Solana-Figueroa et al, 2002;Archer et al, 1982;Ö gren, 1982). Ruotsalainen et al (2000) report mild impairments in response inhibition in animals 3 weeks following a neurotoxic regimen of PCA, but no impairment in a 5-choice serial reaction time task of attention. We are unaware of any studies showing lasting memory impairments in animals following 5-HT depletion by PCA.…”

Section: Discussionmentioning

confidence: 99%

Impaired Object Recognition Memory Following Methamphetamine, but not p-Chloroamphetamine- or d-Amphetamine-Induced Neurotoxicity

Belcher

O’Dell

Marshall

2005

Neuropsychopharmacol

106

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Repeated moderate doses of methamphetamine (mAMPH) damage forebrain monoaminergic terminals and nonmonoaminergic cells in somatosensory cortex, and impair performance in a novelty preference task of object recognition (OR). This study aimed to determine whether the memory deficit seen after a neurotoxic mAMPH regimen results from damage to dopamine (DA) and/or serotonin (5-HT) terminals. Animals were given a neurotoxic regimen of mAMPH, p-chloroamphetamine (PCA, preferentially damages 5-HT terminals), damphetamine (d-AMPH, preferentially damages DA terminals), or saline. After 1 week, animals were trained and tested for OR memory. Rats treated with mAMPH showed no recognition memory during the short-term memory (STM) test, whereas both PCA-and d-AMPH-treated rats showed OR STM scores comparable to controls. After behavioral testing, the specificity of monoaminergic lesions was determined by postmortem [ 125 I]RTI-55 binding to dopamine (DAT) and serotonin (SERT) transporter proteins. Tissue from a separate group of animals killed 3 days after drug treatment was processed for Fluoro-Jade (F-J) fluorescence histochemistry to detect damaged cortical neurons. mAMPH-treated rats showed reductions in striatal DAT and hippocampal (HC) and perirhinal (pRh) SERT, as well as degeneration of neurons in primary somatosensory cortex. In PCA-treated rats, HC and pRh SERT were substantially depleted, but striatal DAT and cortical neuron survival were unaffected. By contrast, d-AMPH-treated animals showed marked depletions in striatal DAT and cortical neurodegeneration, but HC and pRh SERT were unaffected. This pattern of results indicates that no single feature of mAMPH-induced neurotoxicity is sufficient to produce the OR impairments seen after mAMPH treatment.

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“…Mecamylamine also impaired performance in a five-choice serial reaction task in rats (Grottick and Higgins 2000), a finding in agreement with Jones et al (Jones et al 1995) who reported task-specific disruptive effects of mecamylamine in middle aged rats. However, Mirza and Stolerman (Mirza and Stolerman 1998) and Ruotsalainen and colleagues (Ruotsalainen et al 2000) only reported decrements in reaction time, not accuracy following mecamylamine administration in the five-choice serial reaction time task. In nonhuman primates, mecamylamine has been demonstrated to impair delayed matching-to-sample performance (Elrod et al 1988).…”

Section: Introductionmentioning

confidence: 95%

Effects of nicotine and mecamylamine on cognition in rhesus monkeys

et al. 2004

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Rationale-Nicotine and other agonists of nicotinic cholinergic receptors (nAChR) have been shown to improve performance in specific memory domains in rodents and monkeys. Such beneficial effects are observed in preclinical models of age-related cognitive decline, stimulating interest in nAChR ligands as possible therapeutics. Prior work has typically focused on assays of spatial working memory in rodent studies and visual recognition memory in monkey studies.Objective-The current study was conducted to determine the role nAChRs play in multiple types of memory in monkeys.Methods-Rhesus monkeys (N = 6) were trained to perform a battery of 6 behavioral tasks and then serially challenged with acute doses of nicotine (3.2-56 μg/kg, i.m.) and the nAChR antagonist mecamylamine (0.32-1.78 mg/kg, i.m).Results-Nicotine improved performance on tests designed to assay visual recognition memory, spatial working memory and visuo-spatial associative memory while mecamylamine impaired visuospatial associative memory. Ballistic and fine motor performance was not significantly improved by nicotine but fine motor performance was impaired by mecamylamine.Conclusions-Although nicotine may improve performance in multiple domains, effects on visuo-spatial associative memory is the most specifically attributable to nAChR signaling.

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Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion

Cited by 47 publications

References 45 publications

The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

The Pharmacological Characterization of Attentional Processes Using a Two-lever Choice Reaction Time Task in Rats.

Impaired Object Recognition Memory Following Methamphetamine, but not p-Chloroamphetamine- or d-Amphetamine-Induced Neurotoxicity

Effects of nicotine and mecamylamine on cognition in rhesus monkeys

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