Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism

Nakamura, Kazuo; Kurasawa, Mitsue

doi:10.1016/s0014-2999(01)01005-6

Cited by 59 publications

(31 citation statements)

References 54 publications

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“…Similar results of the cognitive enhancing benefits of aniracetam have been found using non-human animals [7]–[11]. In addition to the improvement in cognitive function, aniracetam reduces anxiety in mice [12]. This study found that aniracetam reduces anxiety across three different anxiety tests.…”

Section: Introductionsupporting

confidence: 83%

“…In addition, we administered aniracetam through voluntary oral consumption to more closely mimic how humans would consume the substance. We used the 50 mg/kg dose since it is within the therapeutic range to impact anxiety and learning and memory [7], [12]. If aniracetam is a cognitive enhancer of normal function then we hypothesize that drug-treated animals would show improvement in learning tasks.…”

Section: Introductionmentioning

confidence: 99%

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Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

et al. 2014

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There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.

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Section: Introductionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

et al. 2014

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“…Even if anxiety in the social interaction test qualitatively differs from that assessed on the elevated plus maze test, anxiolytic drugs are effective in both models (File, 1992;Nakamura and Kurasawa, 2001;Crawley, 2007). To gain insight into anxiety-related behaviors in X11L-KO mice, we subjected X11L-KO mice to open field, elevated plus maze, and lightdark transition tests.…”

Section: X11l-ko Mice Do Not Show Altered Anxiety-like Behavior In Comentioning

confidence: 99%

X11-Like Protein Deficiency Is Associated with Impaired Conflict Resolution in Mice

Sano¹,

Ornthanalai²,

Yamada³

et al. 2009

J. Neurosci.

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Understanding how emotion is generated, how conflicting emotions are regulated, and how emotional states relate to sophisticated behaviors is a crucial challenge in brain research. Model animals showing selective emotion-related phenotypes are highly useful for examining these issues. Here, we describe a novel mouse model that withdraws in approach-avoidance conflicts. X11-like (X11L)/Mint2 is a neuronal adapter protein with multiple protein-protein interaction domains that interacts with several proteins involved in modulating neuronal activity. X11L-knock-out (KO) mice were subordinate under competitive feeding conditions. X11L-KO mice lost significantly more weight than cohoused wild-type mice without signs of decreased motivation to eat or physical weakness. In a residentintruder test, X11L-KO mice showed decreased intruder exploration behavior. Moreover, X11L-KO mice displayed decreased marbleburying, digging and burrowing behaviors, indicating aberrant ethological responses to attractive stimuli. In contrast, X11L-KO mice were indistinguishable from wild-type mice in the open field, elevated plus maze, and light/dark transition tests, which are often used to assess anxiety-like behavior. Neurochemical analysis revealed a monoamine imbalance in several forebrain regions. The defective ethological responses and social behaviors in X11L-KO mice were rescued by the expression of X11L under a Camk2a promoter using the Tet-OFF system during development. These findings suggest that X11L is involved in the development of neuronal circuits that contribute to conflict resolution.

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“…Interestingly, even natural levels of anxiety in control rats of both genders were overcome, and sucrose-aniracetam-treated animals showed significantly higher open-arm activity (number of entries) compared with sucrose-treated animals. Although this effect is demonstrated for the first time in a model of fetal ethanol exposure, other authors (Nakamura and Kurasawa, 2001) have reported the anxiolytic effects of aniracetam in many other models, such as the condition fear stress test, forced swim test, and submissive behavioral model (Knapp et al, 2002). These results indicate that aniracetam possesses a wide range of anxiolytic properties, which may be mediated by an interaction between the cholinergic, dopaminergic, and serotonergic systems (Nakamura and Kurasawa, 2001), and is able to reduce fetal ethanol anxiogenic effects in female offspring.…”

Section: Therapeutic Effects Of Aniracetammentioning

confidence: 86%

Aniracetam Reversed Learning and Memory Deficits Following Prenatal Ethanol Exposure by Modulating Functions of Synaptic AMPA Receptors

Vaglenova

Pandiella

Wijayawardhane

et al. 2007

Neuropsychopharmacol

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Specific pharmacological treatments are currently not available to address problems resulting from fetal ethanol exposure, described as Fetal Alcohol Syndrome or Fetal Alcohol Spectrum Disorders (FASD). The present study evaluated the therapeutic effects of aniracetam against cognitive deficits in a well-characterized and sensitive FASD Sprague-Dawley rat model. Ethanol, administered orally at a moderate dose (4 g/kg/24 h; 38% v/v) during the entire course of pregnancy, caused severe cognitive deficits in offspring. Furthermore, both progeny genders were affected by a spectrum of behavioral abnormalities, such as a delay in the development of the righting reflex, poor novelty seeking behavior, and high anxiety levels in female rats. Cognitive disabilities, monitored in adult rats by a two-way active avoidance task, correlated well with a significant reduction of AMPA (a-amino-3 hydro-5 methyl-isoxazole propionic acid) receptormediated miniature excitatory postsynaptic responses (mEPSCs) in the hippocampus. Administration of aniracetam for 10 days (postnatal days (PND) 18-27), at a dose of 50 mg/kg reversed cognitive deficits in both rat genders, indicated by a significant increase in the number of avoidances and the number of 'good learners'. After the termination of the nootropic treatment, a significant increase in both amplitude and frequency of AMPA receptor-mediated mEPSCs in hippocampal CA-1 pyramidal cells was observed. Significant anxiolytic effects on PND 40 also preceded acquisition improvements in the avoidance task. This study provides evidence for the therapeutic potential of aniracetam in reversing cognitive deficits associated with FASD through positive post-natal modulation of AMPA receptors.

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Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism

Cited by 59 publications

References 54 publications

Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

X11-Like Protein Deficiency Is Associated with Impaired Conflict Resolution in Mice

Aniracetam Reversed Learning and Memory Deficits Following Prenatal Ethanol Exposure by Modulating Functions of Synaptic AMPA Receptors

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