Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)

Nazario, Luiza Reali; Antonioli, Régis; Capiotti, Katiúcia Marques; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Bonan, Carla Denise; Silva, Rosane Souza da

doi:10.1016/j.pbb.2015.06.008

Cited by 34 publications

(22 citation statements)

References 58 publications

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“…As for the SE+CBDt group, there was no effect of CBD treatment on delta activity and post-ictal prostration. Since CBD acts with an inverted U-shaped dose-response curve (Guimaraes et al, 1990; Campos et al, 2012; Levin et al, 2014; Nazario et al, 2015), the higher CBD plasma levels of SE+CBDt could be responsible for the lack of CBD effect on exploratory and electrographic activities after SE, if compared to the single treatment group SE+CBDp, which had lower doses of plasma CBD.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy

et al. 2017

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The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5–4 Hz) and theta (4–10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy

et al. 2017

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“…This is in agreement with previous data showing an inverted U-shaped dose-response curve for CBD on behavioral assessments. The CBD inverted U-shaped curve is seen in pre-clinical tests of anxiety and prepulse inhibition of startle ( Guimaraes et al, 1990 ; Levin et al, 2014 ; Nazario et al, 2015 ). In addition, studies from our group show that only the lowest dose of CBD (1 mg/kg) is effective against the social interaction and contextual fear conditioning deficits in an animal model of schizophrenia ( Levin et al, 2012 ; Almeida et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats

et al. 2016

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Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg) or vehicle (days 2–5). On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements, and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals’ performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg) attenuated the increase in catalepsy behavior and in oral movements – but not the decrease in locomotion – induced by reserpine. CBD (0.5 mg/kg) also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.

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“…36 This activity pattern is also consistent with previous adult zebrafish work that tested the effect of CBD and showed no change in swimming speed or distance, but did show an anxiolytic effect in the novel tank test. 15 CBD has also been shown to act as an anxiolytic in acute mammalian behavioral models. [37][38][39][40][41][42] Care should be taken when attempting to link the effects of cannabinoids to stress and anxiety as it has been shown that activation of the endocannabinoid system can lead to both anxiogenic and anxiolytic responses depending on a number of complex interactions between cannabinoids, receptors, and distinct neural pathways.…”

Section: Effects Of Cannabinoids On Zebrafish Larvaementioning

confidence: 99%

“…9,10 While CBD has a low affinity for CB receptors and has been shown to exert its effects through interactions with other receptors, such as the adenosine and serotonin (5-HT) receptors, 12,13 it too has been shown to have bioactivity in zebrafish. [14][15][16] Studies using adult zebrafish have tested the activity of THC [17][18][19] and CBD 15,16 for various indications. The studies that have used zebrafish larvae have been more limited and have looked at toxicity, 8,20 the behavioral effect of THC, 21 and recently the activity of THC and CBD against a model of nociception.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Uptake, Metabolism, and Behavioral Effects of Cannabinoids on Zebrafish Larvae

et al. 2018

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The Cannabis sativa plant contains numerous phytocannabinoids and terpenes with known or potential biological activity. For decades, plant breeders have been breeding the Cannabis plant to control for a desired ratio of the major cannabinoids. A high-throughput in vivo model to understand the relationship between the chemical composition of different strains and their therapeutic potential then becomes of value. Measuring changes in the behavioral patterns of zebrafish larvae is an established model with which to test the biological activity of neuroactive compounds. However, there is currently little information regarding the uptake kinetics and metabolism of compounds by larvae. In this study, we chose to compare the uptake kinetics and metabolism of Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone or in combination with their effects on larval behavior. We have shown that both compounds have distinct behavioral patterns and concentration response profiles. Additionally, the uptake kinetics observed for each compound appears to correlate with the change in behavior observed in the behavioral assays. When combinations of THC and CBD were tested there were shifts in both the behavioral activity and the uptake kinetics of each compound compared with when they were tested alone. Finally, the THC/CBD-derived metabolites detected in the larvae are similar to those found in mammalian systems. This study thus provides a model for further testing of additional cannabinoids and potentially plant extracts.

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Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)

Cited by 34 publications

References 58 publications

Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy

Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy

Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats

Analysis of the Uptake, Metabolism, and Behavioral Effects of Cannabinoids on Zebrafish Larvae

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