Aniracetam attenuates the 5-HT2 receptor-mediated head-twitch response in rodents as a hallucination model

Tanaka, Yushiro; Nakamura, Kazuo; Kurasawa, Mitsue

doi:10.1002/(sici)1098-2299(199808)44:4<131::aid-ddr1>3.0.co;2-s

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…The vigilance-enhancing effects of aniracetam may be implicated in this action (Martin and Haefely 1993). Although 10 mg/kg aniracetam improves the CRT, it has no effect on the DOI (1 mg/kg s.c.)-induced headtwitch response in rats (Tanaka et al 1998), whereas ritanserin (1 mg/kg p.o.) completely blocks both DOI responses.…”

Section: Discussionmentioning

confidence: 92%

“…Such serotonergic activation may counteract the reduction in neuronal activity induced by 8-OH-DPAT. There is no evidence suggesting direct interaction of aniracetam and its metabolites with 5-HT 1 , 5-HT 2A and 5-HT 3 receptor subtypes (Martin and Haefely 1993;Tanaka et al 1998). In addition to the serotonergic mechanism, the cholinergic activation mechanism of both drugs potentially may also be involved in the improvement of attention deficits and low vigilance (Kawajiri et al 1990;Nakamura and Shirane 1999), since reticulothalamic and cortical cholinergic projections have fundamental roles in attentional and vigilance processes (Robbins 1997;Nakamura et al 1998a).…”

Section: Discussionmentioning

confidence: 99%

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Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Nakamura¹,

Kurasawa²

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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Central serotonergic systems play an important role in regulating mood/emotion, cognition, sleep and wakefulness, appetite and locomotion and body temperature via multiple receptor subtypes. Among them, 5-HT1A and 5-HT2A/2C receptors have opposite effects with respect to certain functions. The aim of the present study was to compare the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2A/2C receptor agonist, on the performance of middle-aged rats in a two-lever choice reaction task that assessed attention and vigilance functions. We also examined the effects of aniracetam, a cognition enhancer, and its major metabolites on the induced performance impairments. 8-OH-DPAT (0.3 mg/kg s.c.) reduced response speed and choice accuracy and increased response omission with a reduction of task-associated motor activity without inducing motor inability or motivational changes. These findings indicate a specific disturbance of attentional and vigilance processes. DOI caused similar impairments at the highest dose tested (3 mg/kg s.c.); at a lower dose (1 mg/kg s.c.), however, it selectively attenuated the response speed, suggesting a selective attention deficit. (-)-Alprenolol, a non-selective 5-HT1A receptor antagonist, and ritanserin, a preferential 5-HT2A receptor antagonist, blocked the 8-OH-DPAT- and DOI-induced performance impairments respectively. Aniracetam ameliorated all the performance deficits, and the metabolites N-anisoyl-GABA and 2-pyrrolidinone partially mimicked the aniracetam effect in the 8-OHDPAT-induced attentional and vigilance impairments. Nefiracetam, another cognition enhancer, improved only the 8-OH-DPAT-induced impairments. Each compound tested alone had no effect on task performance. These results indicate that both serotonergic regulations, possibly via presynaptic 5-HT1A receptors and more likely via postsynaptic 5-HT2A receptors, lead similarly to attention deficits.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Nakamura¹,

Kurasawa²

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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“…It has been reported to be a potent modulator of the glutamatergic (AMPA) and cholinergics systems and to block the N-type calcium current [90]. The serotoninergic system also seems involved [91]. Action on AMPA receptor, where it seems to act as a positive allosteric modulator, has been confirmed recently by its high potency in the kinurenate test [92].…”

Section: D-n-side Chain Modified Derivativesmentioning

confidence: 96%

Design and Study of Piracetam-like Nootropics, Controversial Members of the Problematic Class of Cognition-Enhancing Drugs

Gualtieri

Manetti²,

Romanelli³

et al. 2002

CPD

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Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with head traumas, stroke, age and age-related pathologies. Development of cognition enhancers is still a difficult task because of complexity of the brain functions, poor predictivity of animal tests and lengthy and expensive clinical trials. After the early serendipitous discovery of first generation cognition enhancers, current research is based on a variety of working hypotheses, derived from the progress of knowledge in the neurobiopathology of cognitive processes. Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety. In the present review, after a general discussion of the problems connected with the design and development of cognition enhancers, the class is examined in more detail. Reasons for the problems encountered by nootropics, compounds therapeutically available and those in development, their structure activity relationships and mechanisms of action are discussed. Recent developments which hopefully will lead to a revival of the class are reviewed.

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Recovery of Diminished Mealtime-Associated Anticipatory Behavior by Aniracetam in Aged Rats

Tanaka¹

2000

Pharmacology Biochemistry and Behavior

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Aniracetam attenuates the 5-HT2 receptor-mediated head-twitch response in rodents as a hallucination model

Cited by 6 publications

References 37 publications

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Design and Study of Piracetam-like Nootropics, Controversial Members of the Problematic Class of Cognition-Enhancing Drugs

Recovery of Diminished Mealtime-Associated Anticipatory Behavior by Aniracetam in Aged Rats

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