Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction

Franzen, Jaqueline Maisa; Vanz, Felipe; Werle, Isabel; Guimarães, Francisco Silveira; Bertoglio, Leandro J.

doi:10.1016/j.euroneuro.2022.08.002

Cited by 8 publications

(5 citation statements)

References 91 publications

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“…Regardless of SI exposure, CBD was found to have both antidepressant-and anxiolytic-like effects, in line with previous studies in males [3,[55][56][57][58][59] and females [55,[60][61][62]. For example, CBD decreased anxiety-like behavior in the elevated plus maze [60] and decreased freezing behavior and prevented fear reinstatement in a contextual fear paradigm in adult (3-4 months) female rats [62]. In a genetic rat model of depression, adult females and males treated with 30 mg/kg CBD demonstrated pro-hedonic behavior in the saccharin preference test, increased exploration in the novel object recognition test, and decreased immobility in the FST [55].…”

Section: Discussionsupporting

confidence: 89%

“…Exposure to SI increased immobility in the FST in middle-aged female rats, with no effect on freezing or the time in the center in the open field, further suggesting that SI is associated with depression-like behavior [50] and not anxiety [51][52][53][54]. Regardless of SI exposure, CBD was found to have both antidepressant-and anxiolytic-like effects, in line with previous studies in males [3,[55][56][57][58][59] and females [55,[60][61][62]. For example, CBD decreased anxiety-like behavior in the elevated plus maze [60] and decreased freezing behavior and prevented fear reinstatement in a contextual fear paradigm in adult (3-4 months) female rats [62].…”

Section: Discussionsupporting

confidence: 86%

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Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation

Saad,

Raviv,

Mizrachi Zer-Aviv

et al. 2023

IJMS

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Aging is associated with changes in cognitive and emotional function. Cannabidiol (CBD) has been reported to attenuate stress and anxiety in human and animal studies. In this study, we aimed to assess the therapeutic potential of CBD among middle-aged female rats exposed to social isolation (SI) and the potential involvement of brain-derived neurotrophic factor (BDNF) in these effects. Thirteen-month-old female rats were group-housed (GH) or exposed to social isolation (SI) and treated with vehicle or CBD (10 mg/kg). CBD restored the SI-induced immobility in the forced swim test and the SI-induced decrease in the expression of BDNF protein levels in the nucleus accumbens (NAc). CBD also increased the time that rats spent in the center in an open field, improved spatial training, and increased BDNF expression in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). BDNF expression was found to be correlated with an antidepressant (in the NAc) and an anxiolytic (in the mPFC, BLA, NAc) phenotype, and with learning improvement in the PFC. Together, our results suggest that CBD may serve as a beneficial agent for wellbeing in old age and may help with age-related cognitive decline.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 86%

Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation

Saad,

Raviv,

Mizrachi Zer-Aviv

et al. 2023

IJMS

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“…The animal remained in this chamber for 30 s and then returned to its cage. The US intensity and number selected for memory reinstatement were based on prior studies (Franzen et al, 2019(Franzen et al, , 2022. The post-reinstatement fear extinction retention session (Retest A) consisted of re-exposing each animal to the conditioned context without US presentation for 3 min.…”

Section: Contextual Fear Conditioning Behavioural Procedures and Data...mentioning

confidence: 99%

Ayahuasca‐enhanced extinction of fear behaviour: Role of infralimbic cortex 5‐HT_2A and 5‐HT_1A receptors

Werle,

Nascimento,

dos Santos

et al. 2024

British J Pharmacology

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Background and PurposeAyahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N‐dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA‐treated rats.Experimental ApproachWe focused on the 5‐HT1A and 5‐HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis.Key ResultsA single oral treatment with AYA containing 0.3 mg·kg−1 of DMT increased the within‐session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1‐ and 21‐day‐old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA‐ and vehicle‐treated animals showed no differences when tested in the elevated plus‐maze. The 5‐HT2A receptor antagonist MDL‐11,939 and the 5‐HT1A receptor antagonist WAY‐100635 infused into the infralimbic cortex respectively blocked within‐ and between‐session fear extinction effects resulting from repeated oral administration of AYA.Conclusion and ImplicationsOur findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress‐related disorders.

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“…Moreover, the effect of long-term exposure to THC-and CBD-rich extracts throughout adolescence has already been studied in female rats, and it was shown that the CBD-enriched extract reverts the THC-induced downregulation of the CB1 receptor in the prefrontal cortex [67]. In the fear-conditioning paradigm, aversive memory reconsolidation has been disrupted after CBD treatment in a CB1-dependent manner, even though the contribution of CB2 receptors is still controversial [68][69][70]. We showed that the expression of CB1 and CB2 receptors have not been modulated by the CBD-enriched extract in healthy rats, which may suggest that either the CBD/THC ratio of approximately 20:1 or the dose of both phytocannabinoids used prevented the alteration in the CB1 and CB2 expression reported in other studies.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus

Aguiar

Campos

Isaac

et al. 2023

IJMS

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The endocannabinoid system (eCS) is widely distributed in mammalian tissues and it is classically formed by cannabinoid receptors, endogenous bioactive lipids and its synthesis and degradation enzymes. Due to the modulatory role of eCS in synaptic activity in the Central Nervous System (CNS), phytocannabinoids have been increasingly used for the treatment of neurological disorders, even though little is known in terms of the long-term effect of these treatments on CNS development, mainly in the timeframe that comprises childhood and adolescence. Furthermore, an increased number of clinical trials using full-spectrum Cannabis extracts has been seen, rather than the isolated form of phytocannabinoids, when exploring the therapeutical benefits of the Cannabis plant. Thus, this study aims to evaluate the effect of cannabidiol (CBD)-enriched Cannabis extract on synaptic components in the hippocampus of rats from adolescence to early adulthood (postnatal day 45 to 60). Oral treatment of healthy male Wistar rats with a CBD-enriched Cannabis extract (3 mg/kg/day CBD) during 15 days did not affect food intake and water balance. There was also no negative impact on locomotor behaviour and cognitive performance. However, the hippocampal protein levels of GluA1 and GFAP were reduced in animals treated with the extract, whilst PSD95 levels were increased, which suggests rearrangement of glutamatergic synapses and modulation of astrocytic features. Microglial complexity was reduced in CA1 and CA3 regions, but no alterations in their phagocytic activity have been identified by Iba-1 and LAMP2 co-localization. Collectively, our data suggest that CBD-enriched Cannabis treatment may be safe and well-tolerated in healthy subjects, besides acting as a neuroprotective agent against hippocampal alterations related to the pathogenesis of excitatory and astrogliosis-mediated disorders in CNS.

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Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction

Cited by 8 publications

References 91 publications

Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation

Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation

Ayahuasca‐enhanced extinction of fear behaviour: Role of infralimbic cortex 5‐HT_2A and 5‐HT_1A receptors

Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus

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Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction

Cited by 8 publications

References 91 publications

Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation

Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation

Ayahuasca‐enhanced extinction of fear behaviour: Role of infralimbic cortex 5‐HT2A and 5‐HT1A receptors

Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus

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Product

Resources

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Ayahuasca‐enhanced extinction of fear behaviour: Role of infralimbic cortex 5‐HT_2A and 5‐HT_1A receptors