Riluzole Does Not Affect Hippocampal Synaptic Plasticity and Spatial Memory, Which Are Impaired by Diazepam in Rats

Sasaki-Hamada, Sachie; Sacai, Hiroaki; Sugiyama, Azusa; Iijima, Takahiro; Saitoh, Akiyoshi; Inagaki, Masumi; Yamada, Mitsuhiko; Oka, Jun

doi:10.1254/jphs.13052sc

Cited by 12 publications

(6 citation statements)

References 14 publications

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“… a Subgroup analysis of RCT by Spangler et al (2020). 13 b Riluzole was increased to 200 mg/day for participants not demonstrating at least a 10‐point improvement on the PCL‐S at 2 weeks. c Fluvoxamine, clomipramine, escitalopram, and fluoxetine were used.…”

Section: Resultsmentioning

confidence: 99%

“…Spangler et al 13 Low Low Some Low Low Low Pittenger et al 19 Low Low Some Low Some Some Emamzadehfard et al 20 Low Low Some Low Low Low Grant et al 12 Low Low Some Low Low Some study had a low risk of bias except for "bias due to missing outcome data" (Table 2). However, there were no statistically significant differences in any adverse events between the two groups.…”

Section: Overall Risk Of Biasmentioning

confidence: 99%

“… 9 Although benzodiazepines are associated with several side effects, including motor incoordination and memory/cognitive dysfunction, 10 , 11 , 12 riluzole does not impair these functions. 9 , 13 Furthermore, recent studies showed that riluzole enhanced extinction learning of fear memory, 14 and may also have an inhibitory effect on fear memory reconsolidation. 15 These results suggest riluzole could be an ideal concomitant medication with exposure therapy.…”

Section: Introductionmentioning

confidence: 99%

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Effects of riluzole on psychiatric disorders with anxiety or fear as primary symptoms: A systematic review

Kawashima

Yamada

Furuie

et al. 2023

Neuropsychopharm Rep

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AimPrevious behavioral pharmacology studies involving rodents suggested riluzole had potential to be an ideal psychotropic drug for psychiatric disorders with anxiety or fear as primary symptoms. Several clinical studies have recently been conducted. The purpose of this study was to gather information about the efficacy and tolerability of riluzole for patients with those symptoms.MethodsWe searched PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane database from inception until April 2021, and performed manual searches for additional relevant articles. This review included: (1) studies involving participants that were patients with generalized anxiety disorder (GAD), social anxiety disorder, panic disorder, obsessive‐compulsive disorder (OCD), posttraumatic stress disorder (PTSD), acute stress disorder, or phobias; and (2) randomized controlled trials (RCTs) or intervention studies (e.g., single arm trials) examining the effects and safety of riluzole.ResultsOf the 795 identified articles, four RCTs, one RCT subgroup‐analysis, and three open‐label trials without control groups met the inclusion criteria. Most trials evaluated the efficacy of riluzole as an augmentation therapy with selective serotonin reuptake inhibitors and other antidepressants for PTSD, OCD, or GAD. However, there was insufficient evidence to confirm the effects of riluzole for patients with these psychiatric disorders. Most trials demonstrated adequate study quality.ConclusionsThis review found insufficient evidence to confirm the effects of riluzole for psychiatric disorders with anxiety or fear as primary symptoms. It would be worthwhile to conduct studies that incorporate novel perspectives, such as examining the efficacy of riluzole as a concomitant medication for psychotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Overall Risk Of Biasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of riluzole on psychiatric disorders with anxiety or fear as primary symptoms: A systematic review

Kawashima

Yamada

Furuie

et al. 2023

Neuropsychopharm Rep

Self Cite

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“…It was also suggested that sheep may have spent more time eating and consequently less time displaying vigilance behavior due to diazepam increasing appetite and not due to an anxiolytic effect of the drug [59,60]. Further, studies in rats have found that diazepam can impair spatial memory or learning [61,62], which may confound responses during attention bias testing if a sheep no longer associates the previous location of the dog with the threat of a dog and does not localize their attention accordingly. Previous studies administering diazepam to sheep have given inconsistent results, with some [32] but not all studies [30,31] observing behavioral responses that are expected to indicate a calm state, such as decreased vigilance during an arena test, decreased agitation in an isolation box and a reduced startle response.…”

Section: Discussionmentioning

confidence: 99%

Attention Bias Test Measures Negative But Not Positive Affect in Sheep: A Replication Study

Monk

Dickson

et al. 2020

Animals

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An attention bias test has been developed as a measure of negative affective states in sheep. The test measures an individual’s allocation of attention between a threatening (previous location of a dog) and positive (conspecific photo) stimulus over a 3 min period. This study replicated a previously inconclusive study, to determine whether the test could assess positive affective states under more controlled conditions and with a younger population of animals. Pharmacological treatments were used to induce anxious, calm, happy, and control affective states prior to entering the attention bias test arena (n = 20/treatment). We hypothesized that sheep in positive and negative affective states could be differentiated using key measures of attention during testing, including vigilance (head at or above shoulder height) and duration looking towards the valenced stimuli. Anxious sheep were more vigilant than control animals during attention bias testing as predicted (linear mixed effects model, p = 0.002), but the positive groups did not differ from controls (p > 0.05). There was no effect of treatment on looking behaviors (p > 0.05). We suggest this attention bias test paradigm can assess negative but not positive affect in sheep and that modifications to the ethogram or stimuli are needed to more clearly characterize the direction of attention during testing.

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“…For example, spatial memory or learning may confound animal responses if a test subject no longer associates the previous location of the dog with the threat of a dog and does not localise their attention accordingly. This potentially confounding factor is important to consider when using pharmacological models that may have an impact on spatial memory or learning, as may be the case for diazepam (Brioni and Arolfo 1992;Sasaki-Hamada et al 2013). It may be worthwhile exploring options to balance stimulus presentation times in the attentionbias test in a way that does not increase the intensity of the threat, such as by using a photograph of a dog instead of or in conjunction with a live dog.…”

Section: Stimulus Duration and Intensitymentioning

confidence: 99%

Future application of an attention bias test to assess affective states in sheep

Monk

Campbell

2023

Anim. Prod. Sci.

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The affective states of animals comprise a key aspect of welfare that can be difficult to assess. An attention-bias test was developed for sheep, which assessed allocation of attention between a predator threat and a food reward, as a potential measure of affective state. The method was pharmacologically validated as a measure of anxiety-like states, finding that 'anxious' sheep were more vigilant, less likely to feed and spent more time looking towards the previous location of a dog than did 'calm' sheep. Across six further validation studies, the method was modified and explored as a measure of other types of affective states. This perspective article aims to provide guidance on what the method can tell us about affective state and make recommendations for further research by using this approach. Evidence was strongest across the studies for the test as a measure of anxiety-like states, but it is clear that there are other factors affecting animal behaviour during testing that need to be further investigated. One study showed potential for a modified method to assess depression-like states in sheep, while the impact of chronic stress on affect and attention bias remains unclear. It is likely that the test cannot be used to measure positive affect in sheep without further modification, due to the fear-eliciting nature of the test. Versions of the method using food as a positive stimulus allow for a clearer interpretation of attention than do versions using a conspecific photograph, and are recommended for use in future studies where appetite is not expected to be a confounding factor. In this context, vigilance behaviour may indicate trait anxiety or fearfulness, while other measures of attention may be more sensitive to transient changes in affect. Modifications to the method are suggested to allow for a clearer characterisation of attention in livestock species and to improve the practical application of the test. Overall, the attention-bias test shows promise as a measure of negative affective states, but the method is still very new and further research is needed to better determine its potential use as a welfare-assessment tool.

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Riluzole Does Not Affect Hippocampal Synaptic Plasticity and Spatial Memory, Which Are Impaired by Diazepam in Rats

Cited by 12 publications

References 14 publications

Effects of riluzole on psychiatric disorders with anxiety or fear as primary symptoms: A systematic review

Effects of riluzole on psychiatric disorders with anxiety or fear as primary symptoms: A systematic review

Attention Bias Test Measures Negative But Not Positive Affect in Sheep: A Replication Study

Future application of an attention bias test to assess affective states in sheep

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