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

Saad, Nadya; Raviv, Danielle; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

doi:10.3390/ijms242015492

IJMS

2023

DOI: 10.3390/ijms242015492

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

Nadya Saad,

Danielle Raviv,

Tomer Mizrachi Zer-Aviv

et al.

Abstract: 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 … Show more

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2024

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Cited by 4 publications

References 83 publications

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Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans

Wang,

Arnold

2024

GeroScience

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There is a significant global upsurge in the number and proportion of older persons in the population. With this comes an increasing prevalence of age-related conditions which pose a major challenge to healthcare systems. The development of anti-ageing treatments may help meet this challenge by targeting the ageing process which is a common denominator to many health problems. Cannabis-like compounds (cannabinoids) are reported to improve quality of life and general well-being in human trials, and there is increasing preclinical research highlighting that they have anti-ageing activity. Moreover, preclinical evidence suggests that endogenous cannabinoids regulate ageing processes. Here, we review the anti-ageing effects of the cannabinoids in various model systems, including the most extensively studied nematode model, Caenorhabditis elegans. These studies highlight that the cannabinoids lengthen healthspan and lifespan, with emerging evidence that they may also hinder the development of cellular senescence. The non-psychoactive cannabinoid cannabidiol (CBD) shows particular promise, with mechanistic studies demonstrating it may work through autophagy induction and activation of antioxidative systems. Furthermore, CBD improves healthspan parameters such as diminishing age-related behavioural dysfunction in models of both healthy and accelerated ageing. Translation into mammalian systems provides an important next step. Moreover, looking beyond CBD, future studies could probe the multitude of other cannabis constituents for their anti-ageing activity.

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Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans

Wang,

Arnold

2024

GeroScience

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Long-term social isolation impairs learning in a two-way active avoidance task in female rats

Krupina,

Khlebnikova

2024

Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova

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In socially living species, including humans, social contacts’ deficit provokes chronic stress development, leading to disorders in the psychoemotional sphere, cognitive impairment, etc. Previously, we showed that spatial memory and passive avoidance impairments in rats exposed to months-long social isolation (SI) from an early age are more pronounced in females compared to males. There is lack research on females. This study aimed to evaluate learning in the two-way avoidance paradigm using the conditioned active avoidance reflex (CAAR) test and to assess skill retention in female rats exposed to SI, which started after the pups were taken from their dams and lasted for up to ten months. After 6.5 months of SI, rats were trained in the CAAR test when their anxiety level and grooming expression were lower than in rats housed in groups. Rats exposed to SI performed fewer avoidance but more escape responses and were less likely to achieve the learning criterion. In isolated rats compared to control rats, the escape latency was heightened, and the maximum number of avoidance reactions in a row was less after 24 hours after training. After 2 months after training, no differences in CAAR retention were revealed between rats kept in different housing conditions. After 10 months of SI, rat blood serum corticosterone levels were lower than in rats in the control group. The findings show worse learning and skill retention one day following training in the CAAR test in rats under the influence of long-term SI.

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Cannabidiol Modulates Neuroinflammatory Markers in a PTSD Model Conducted on Female Rats

Portugalov,

Peled,

Zorin

et al. 2024

Biomolecules

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Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric condition closely linked to neuroinflammation, with a higher prevalence in women. Cannabidiol (CBD), a non-psychoactive cannabinoid, has shown promise as a potential treatment for PTSD. In this study, we used a PTSD model in which female rats were subjected to a severe foot shock followed by contextual situational reminders (SRs). Testing was conducted one month after exposure. The rats received daily CBD injections for three weeks during the SRs, from days 7 to 28. Two days after the final SR, the rats underwent five extinction trials, followed by the forced swim test (FST). After a five-day rest period, the rats were sacrificed, and brain tissues from the medial prefrontal cortex (mPFC) and ventral subiculum (vSUB) were analyzed for inflammatory markers. Chronic CBD treatment reversed impairments in fear extinction caused by shock and SR. It also reduced learned helplessness in the FST and decreased the upregulation of mPFC-il1β induced by shock and SRs. Additionally, exposure to shock and SRs downregulated mPFC-il6 while upregulating vSUB-il6. CBD treatment further downregulated il6 expression in the vSUB compared to the vehicle groups. Our findings show that CBD effectively inhibited the development of PTSD-like behaviors and suppressed neuroinflammation in the mPFC.

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

Cited by 4 publications

References 83 publications

Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans

Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans

Long-term social isolation impairs learning in a two-way active avoidance task in female rats

Cannabidiol Modulates Neuroinflammatory Markers in a PTSD Model Conducted on Female Rats

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