Traumatic Stress, Chronic Ethanol Exposure, or the Combination, Alter Cannabinoid System Components in Reward and Limbic Regions of the Mouse Brain

Piggott, Veronica M; Lloyd, Scott C; Matchynski, James I.; Perrine, Shane A.; Conti, Alana C.

doi:10.3390/molecules26072086

Cited by 7 publications

(3 citation statements)

References 106 publications

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“…During adolescence, many brain areas are known to undergo functional and structural reorganization. Among the primary structures involved in stress, emotional regulation, motivation and reward, are the mPFC and the amygdala, which are vulnerable to the effects of chronic stress and alcohol exposure [45]. The ECS is widely expressed in both brain regions [46], and this system is also undergoing dynamic changes during adolescence [47,48].…”

Section: Discussionmentioning

confidence: 99%

Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats

et al. 2022

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(1) Background: Negative experiences during adolescence increase the vulnerability to develop mental disorders later in life. A better understanding of the mechanisms underlying these long-term alterations could help to identify better therapeutic interventions. (2) Methods: Adolescent male Wistar rats were used to explore the effects of repeated stress and alcohol exposure on anxiety-like behaviors, plasma corticosterone levels and the gene expression of the endocannabinoid system (ECS) and other relevant signaling systems (glutamatergic, corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY)) in the amygdala and the medial prefrontal cortex (mPFC). (3) Results: Overall, both stress and alcohol induced anxiety-like behaviors, but only the alcohol-exposed rats displayed increased plasma levels of corticosterone. In the amygdala, there was a general deficit in the gene expression of the ECS and increases in the mRNA levels of certain subunits of glutamate receptors. Interestingly, there were significant interaction effects between stress and alcohol on the expression of the NMDA receptor subunits. In addition, increased mRNA levels of the CRH receptor were observed in alcohol-exposed rats. In the mPFC, alcohol exposure was associated with an increase in the gene expression of the ECS. By contrast, the combination of stress and alcohol produced opposite effects. (4) Conclusions: In summary, early stress and alcohol exposure induced long-term anxiety-like behavior in male rats but different mechanisms are involved in these maladaptive changes in the brain.

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Section: Discussionmentioning

confidence: 99%

Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats

et al. 2022

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“…These substances in particular warrant mention as both acute and chronic use can alter eCB functioning. For example, AEA levels in the corticolimbic brain regions (i.e., amygdala and frontal cortex) increase after chronic alcohol (Piggott et al, 2021), nicotine (González et al, 2002), and cannabis exposure in rodents (Di Marzo et al, 2002). While we found a significant difference between genotype groups in lifetime cannabis use, eliminating those who used the most (>100 uses) from our analyses did not change our results.…”

Section: Discussionmentioning

confidence: 99%

A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults

Zabik

Iadipaolo

Marusak

et al. 2021

J of Neuroscience Research

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Poor fear extinction learning and recall are linked to the development of fear‐based disorders, like posttraumatic stress disorder, and are associated with aberrant activation of fear‐related neural circuitry. This includes greater amygdala activation during extinction learning and lesser hippocampal and ventromedial prefrontal cortex (vmPFC) activation during recall. Emerging data indicate that genetic variation in fatty acid amide hydrolase (FAAH C385A; rs324420) is associated with increased peripheral endocannabinoid (eCB) levels and lesser threat‐related amygdala reactivity. Preclinical studies link increased eCB signaling to better extinction learning and recall, thus FAAH C385A may protect against the development of trauma‐related psychopathology by facilitating extinction learning. However, how this FAAH variant affects fear extinction neural circuitry remains unknown. In the present study, we used a novel, immersive‐reality fear extinction paradigm paired with functional neuroimaging to assess FAAH C385A effects on fear‐related neural circuitry and conditioned fear responding (US expectancy ratings, subjective units of distress, and skin conductance responding) in healthy adults from an urban area (Detroit, MI; N = 59; C/C = 35, A‐carrier = 24). We found lesser amygdala activation in A‐allele carriers, compared to C/C homozygotes, during early extinction recall. Likewise, we found lesser dorsal anterior cingulate cortex and greater hippocampus activation in early extinction learning in A‐carriers compared to C/C homozygotes. We found no effects of FAAH C385A on vmPFC activation or behavioral fear indices. These data support and extend previous findings that FAAH genetic variation, associated with increased eCB signaling and subsequent enhanced fear extinction, may predict individual differences in successful fear learning.

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“…Thus, the present study demonstrated the involvement of CB1rs of the cerebellum in PTSD-like behaviors, showing significant sex differences that could explain, at least in part, the increased susceptibility of females to stress, anxiety, and PTSD [202]. However, in the mild single prolonged stress animal model of PTSD, the quantification of cannabinoid components (AEA, 2-AG, FAAH and MAGL) showed no differences between the model-exposed and control animals in different brain regions involved in mood and emotional processing [203].…”

Section: Animal Studiesmentioning

confidence: 94%

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Navarro

Gasparyan

Navarrete

et al. 2022

IJMS

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The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.

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Traumatic Stress, Chronic Ethanol Exposure, or the Combination, Alter Cannabinoid System Components in Reward and Limbic Regions of the Mouse Brain

Cited by 7 publications

References 106 publications

Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats

Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats

A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

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