NMDA antagonists disrupt timing behaviour in rats

Dj, Sanger

doi:10.1097/00008877-199212000-00006

Cited by 37 publications

(34 citation statements)

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“…the 5-CSRT and DRL24 tasks. In particular, we were interested in examining the influence of these 5-HT antagonists in combination with the NMDA antagonist dizocilpine, which clearly impairs performance in such tasks (Welzl et al 1989;Sanger 1992;Stephens and Cole 1996;Higgins et al 2003). For the 5-CSRTT experiments, we also included the novel NR2B subunit-selective antagonist Ro 63-1908 (Gill et al 2002), which has a particularly striking effect on premature responding in this task.…”

Section: Discussionmentioning

confidence: 99%

“…Behavioural disturbances induced by NMDA receptor blockade are particularly pronounced in tests that require a degree of inhibitory control. For example, in behavioural situations requiring animals to tolerate a delay before making a response, such as performing the 5-choice serial reaction time task (5-CSRTT; Robbins 2002) and operant responding maintained by a differential low rate of responding (DRL), dizocilpine pretreatment increases the probability of the animals making premature responses (Welzl et al 1991;Sanger 1992;Stephens and Cole 1996;. We have extended these observations to the recently described NR2B subtype selective NMDA antagonist Ro 63-1908 (Gill et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism

et al. 2003

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In the present series of studies, we have investigated the effects of antagonists selective for the 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors on motor and 'impulsive'-type behaviours elicited by the non-competitive N-methyl- d-aspartate (NMDA) antagonist dizocilpine. The selective 5-HT(2A) receptor antagonist M100,907 (0.5 mg/kg) attenuated the hyperlocomotion and stereotypy produced by dizocilpine (0.1-0.3 mg/kg). The selective 5-HT(2B) receptor antagonist SB215,505 (3 mg/kg) and the selective 5-HT(2C) receptor antagonist SB242,084 (0.5 mg/kg) had no effect against either measure, except that SB242,084 produced a small potentiation of the hyperactivity response. Dizocilpine (0.03 mg/kg) increased premature responding in rats performing the 5-choice serial reaction time task (5-CSRTT), and increased response frequency consequently reducing the mean inter-response time (IRT) and efficiency of responding in a DRL24 task. M100,907 (0.5 mg/kg) attenuated each of these effects, as well as the increased premature responding produced by the NMDA NR2B selective antagonist Ro 63-1908 (1 mg/kg) in the 5-CSRTT. In contrast SB242,084 (0.5 mg/kg) did not attenuate the dizocilpine-induced premature responding or increased responding in the DRL24 task. Rather, SB242,084 (0.05-0.5 mg/kg) produced qualitatively similar effects to dizocilpine, increasing premature responding and reducing IRT. The results suggest that 5-HT(2A) receptor antagonists may normalise certain 'impulsive' behaviours produced by NMDA receptor hypofunction. The 5-HT(2C) receptor antagonist SB242,084 failed to exert equivalent effects, rather a trend toward exacerbation of the behavioural changes produced by dizocilpine was apparent.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism

et al. 2003

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“…[30][31][32] For example, in a differential reinforcement of a low-rate 15-s (DRL-15 s), MK-801 (0.1-0.2 mg/kg) produced markedly higher rates of lever pressing, especially during a period of interresponse times of 5 s or less, suggesting that NMDA receptor antagonists disrupt timing behavior, leading to a large proportion of premature responses. 30) Moreover, MK-801 (0.1 mg/kg) increased the response rate of schedule-controlled behavior in rats. 33) It is likely that the stimulatory effects of MK-801 may be mediated through the activation of the central dopaminergic system.…”

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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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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“…A fraction of animals (about 40%) were very clearly stimulated by 10-40mg/kg eliprodil, but the inter-animal variability was so high that the overall increase in locomotion was not statistically significant. We have noticed before that mice can be classified either as "responders" or "non-responders" to the low affinity NMDA channel blocker, dextromethorphan , and it is interesting to note that wide variations also occurred in the response rates of individual animals given phencyclidine, in a differential reinforcement paradigm (Sanger, 1992). Why eliprodil is motorgenic in some individuals and not others is not clear, but it may be related to its complex profile of interaction with other transmitter systems, including 6 receptors as well as noradrenergic and tryptaminergic systems (Chenard et al, 1991;Hashimoto and London, 1995).…”

Section: Discussionmentioning

confidence: 99%

Motor actions of eliprodil in the normal and monoamine-depleted mouse: A role in the treatment of Parkinson's disease?

Brooks

Kaur

Starr

et al. 1996

J. Neural Transmission

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The non-competitive NMDA polyamine site antagonist, eliprodil, was examined for its effects on exploratory activity in non-habituated mice and for its antiakinetic potential in reserpine-treated mice. A low dose of eliprodil (5 mg/kg) weakly stimulated locomotion in naive animals, whilst higher doses depressed rearing (20-40 mg/kg) and grooming (40 mg/kg), consistent with a sedative action. At no dose did eliprodil cause ataxia. In 24 h reserpine-treated mice, eliprodil (10-40 mg/kg) reversed akinesia, but this effect was subject to considerable inter-animal variation and was not statistically significant. Eliprodil did not alter the motor recovery elicited by the dopamine D1 agonist SKF 38393, or the dopamine D2 agonist RU 24213, and suppressed the motor stimulation induced by L-DOPA. These results indicate that eliprodil displays a far lower propensity than many other NMDA receptor antagonists for disturbing posture and gait, but lacks the essential motor stimulant action required to make it a safe and effective antiparkinsonian agent, at least in the reserpine-treated mouse model of Parkinson's disease.

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NMDA antagonists disrupt timing behaviour in rats

Cited by 37 publications

References 0 publications

The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism

The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism

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

Motor actions of eliprodil in the normal and monoamine-depleted mouse: A role in the treatment of Parkinson's disease?

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