Mnemonic and behavioral effects of biperiden, an M1-selective antagonist, in the rat

Popelíková, Anna; Bahník, Štěpán; Lobellová, Veronika; Svoboda, Jan; Stuchlı́k, Aleš

doi:10.1007/s00213-018-4899-3

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…The visible platform test was performed to detect the effect of the modified 2-VO on the visual and sensorimotor abilities in rats ( Popelikova et al, 2018 ). There was no significant difference in swimming speed between the three groups [ F (2, 57) = 0.02281, p = 0.9775; Figure 2F ], indicating that there was no damage to sensorimotor ability.…”

Section: Resultsmentioning

confidence: 99%

Enriched environment attenuates hippocampal theta and gamma rhythms dysfunction in chronic cerebral hypoperfusion via improving imbalanced neural afferent levels

Zheng,

Peng,

Cui

et al. 2023

Front. Cell. Neurosci.

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Chronic cerebral hypoperfusion (CCH) is increasingly recognized as a common cognitive impairment-causing mechanism. However, no clinically effective drugs to treat cognitive impairment due to CCH have been identified. An abnormal distribution of neural oscillations was found in the hippocampus of CCH rats. By releasing various neurotransmitters, distinct afferent fibers in the hippocampus influence neuronal oscillations in the hippocampus. Enriched environments (EE) are known to improve cognitive levels by modulating neurotransmitter homeostasis. Using EE as an intervention, we examined the levels of three classical neurotransmitters and the dynamics of neural oscillations in the hippocampus of the CCH rat model. The results showed that EE significantly improved the balance of three classical neurotransmitters (acetylcholine, glutamate, and GABA) in the hippocampus, enhanced the strength of theta and slow-gamma (SG) rhythms, and dramatically improved neural coupling across frequency bands in CCH rats. Furthermore, the expression of the three neurotransmitter vesicular transporters—vesicular acetylcholine transporters (VAChT) and vesicular GABA transporters (VGAT)—was significantly reduced in CCH rats, whereas the expression of vesicular glutamate transporter 1 (VGLUT1) was abnormally elevated. EE partially restored the expression of the three protein levels to maintain the balance of hippocampal afferent neurotransmitters. More importantly, causal mediation analysis showed EE increased the power of theta rhythm by increasing the level of VAChT and VGAT, which then enhanced the phase amplitude coupling of theta-SG and finally led to an improvement in the cognitive level of CCH. These findings shed light on the role of CCH in the disruption of hippocampal afferent neurotransmitter balance and neural oscillations. This study has implications for our knowledge of disease pathways.

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Section: Resultsmentioning

confidence: 99%

Enriched environment attenuates hippocampal theta and gamma rhythms dysfunction in chronic cerebral hypoperfusion via improving imbalanced neural afferent levels

Zheng,

Peng,

Cui

et al. 2023

Front. Cell. Neurosci.

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Cholinergic models of memory impairment in animals and man: scopolamine vs. biperiden

Blokland¹

2022

Behavioural Pharmacology

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Scopolamine has been used as a pharmacologic model for cognitive impairments in dementia and Alzheimer’s disease. The validity of this model seems to be limited because findings in animals do not readily translate to novel treatments in humans. Biperiden is also a cholinergic deficit model for cognitive impairments but specifically blocks muscarinic M1 receptors. The effects of scopolamine and biperiden (and pirenzepine) are compared in animal studies and related to findings in humans. It is concluded that the effects on cognitive functions are different for scopolamine and biperiden, and they should be considered as different cognitive deficit models. Scopolamine may model more advanced stages of Alzheimer’s disease whereas biperiden may model the early deficits in declarative memory in aging and mild cognitive impairment.

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Biperiden Selectively Impairs Verbal Episodic Memory in a Dose- and Time-Dependent Manner in Healthy Subjects

Borghans

Sambeth²,

Blokland³

2019

J Clin Psychopharmacol

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Purpose/Background Biperiden is a muscarinic antagonist that produces memory impairments without impairing attention or motor functions in healthy subjects. It has been suggested that a biperiden-induced memory deficit could model age- and dementia-related memory impairments. The goal of the current study was to determine the dose- and time-dependent effects of biperiden on cognition in healthy volunteers. Methods/Procedures Twenty-one healthy volunteers participated in a placebo-controlled, 3-way, crossover study. After a baseline test, cognitive performance was tested at 3 time points after a single dose of biperiden 2 or 4 mg, or placebo. Episodic memory was measured using a 15-word verbal learning task (VLT). Furthermore, n-back tasks, a sustained attention to response task and a reaction time task were used, as well as subjective alertness and a side effects questionnaire. In addition, blood serum values and physiological measures were taken. Findings/Results Biperiden decreased the number of words recalled in immediate and delayed recall of the VLT 90 minutes after drug intake. A dose-dependent impairment was found for the delayed recall, whereas the immediate recall was equally impaired by the 2 doses. Biperiden did not affect the performance on the VLT 4 hours after administration. Performance in the n-back task and the sustained attention to response task were not affected by biperiden at any time point. Both doses were well tolerated as reported side effects were mild at T max and were minimal at the other time points. Implications/Conclusions Biperiden exerts effects on episodic memory without negatively affecting other cognitive performance and behavioral measures that were assessed in this study. The data provide further evidence that biperiden has selective effects on cognition, even after a high dose.

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Mnemonic and behavioral effects of biperiden, an M1-selective antagonist, in the rat

Abstract: Based on our results, we do not recommend biperiden as a reliable tool for modeling cognitive impairment.

Cited by 3 publications

References 39 publications

Enriched environment attenuates hippocampal theta and gamma rhythms dysfunction in chronic cerebral hypoperfusion via improving imbalanced neural afferent levels

Enriched environment attenuates hippocampal theta and gamma rhythms dysfunction in chronic cerebral hypoperfusion via improving imbalanced neural afferent levels

Cholinergic models of memory impairment in animals and man: scopolamine vs. biperiden

Biperiden Selectively Impairs Verbal Episodic Memory in a Dose- and Time-Dependent Manner in Healthy Subjects

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