Inhibition of the fatty acid amide hydrolase changes behaviors and brain catecholamines in a sex-specific manner in rats exposed to chronic unpredictable stress

Jankovic, Milica; Spasojević, Nataša; Ferizović, Harisa; Stefanović, Bojana; Dronjak, Sladjana

doi:10.1016/j.physbeh.2020.113174

Cited by 22 publications

(13 citation statements)

References 76 publications

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“…While disturbed serotonergic system is often observed in zebrafish models of stress 27 , 44 , serotonin was unaltered by PCUS here, likely because serotonergic changes may occur earlier then norepinephrinergic, given that all previous fish studies used shorter CUS models, whose neurochemical responses highly depend on the duration of stress 27 . Similarly, in rats, 6-week CUS decreases norepinephrine in PFC, hippocampus and hypothalamus, and increases dopamine levels in the same brain areas 45 , whereas 7-day CUS decreases dopamine and serotonin levels in PFC, striatum and hippocampus 46 . Norepinephrine levels rise in plasma of depressed patients 47 , 48 , and correlate with depressive and anxiety symptoms in healthy subjects 49 .…”

Section: Discussionmentioning

confidence: 84%

Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model

Demin

Колесникова

Galstyan

et al. 2021

Sci Rep

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Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish (Danio rerio) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism.

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Section: Discussionmentioning

confidence: 84%

Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model

Demin

Колесникова

Galstyan

et al. 2021

Sci Rep

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“…Lastly, a number of studies assessed sex differences with respect to FAAH. While two studies found significant sex differences in FAAH, three studies found no differences in FAAH between the sexes [49,50,62,65,67,68]. Evidently, the data on sex differences in FAAH are mixed, which could be due to differences in the animal model or species strain.…”

Section: Discussionmentioning

confidence: 96%

“…The authors also assayed FAAH enzymatic activity using [ 3 H]-anandamide as a substrate, which showed that URB597 effectively produced inhibition of FAAH activity in the midbrain, striatum and hippocampus. Similarly, Jankovic et al studied male and female rats exposed to CUS [62]. The authors found that CUS increased depressive-like behaviors as measured by increased immobility time on the FST in both males and females.…”

Section: Antidepressant-like Effects Of Urb597 Urb694 and Other Faahmentioning

confidence: 97%

“…The brain regions that are most influenced by FAAH inhibitors are the PFC, hippocampus, and striatum; dysregulated FAAH activity in these regions could explain MDD symptoms such as loss of motivation, cognitive dysfunction, and anhedonia [53]. Moreover, preclinical studies of FAAH inhibition also reveal some sex differences in depressive phenotypes; still, FAAH inhibitors seem to effectively reduce depressive-like behaviors in both male and female animals [62,65,68]. A number of studies provided evidence of dose-response effects that must be further studied and will be relevant for new clinical trials [56,57,60,69,75].…”

Section: Antidepressant-like Effects Of Urb597 Urb694 and Other Faahmentioning

confidence: 99%

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Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

Rafiei

Kolla

2021

IJMS

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Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

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“…These samples, prepared in this way, were kept at −20°C until analysis. Using the method proposed by Lowry et al (1951), concentration of protein in the samples was determined, and Western blot analysis was done as previously described [11]. The respective primary antibodies that were used for the specific labeling of the given proteins are: for TH (dilution 1:1,000, Catalog No.…”

Section: Protein Isolation and Western Blot Analysismentioning

confidence: 99%

Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats

Ferizović¹,

Spasojević²,

Jankovic³

et al. 2021

Pharmacology

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Introduction: The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS). Material and Methods: Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol. Catecholamines’ plasma levels and catecholamines’ levels in adrenal medulla were examined using Elabscience ELISA kits. Western blot analysis was used to detect the protein in the medulla. Results: The results of our experiment showed that adrenal weights and catecholamine of unstressed control were higher in females and that CUS induced further enlargement of adrenal glands and catecholamine content and its synthesis compared to male rats. CUS caused an increase of plasma norepinephrine and depletion of norepinephrine content as well as unchanged synthesis and degradation of catecholamine in the adrenal medulla of male rats. URB597 reduced enlarged adrenals and catecholamine content and its synthesis in stressed female rats. URB597 reduces increased plasma norepinephrine and restores its content in the adrenal medulla, unchanging the expression of enzyme synthesis, while reduced protein levels of monoamine oxidase A in male rats are exposed to CUS. Discussion: Our results support the role of endocannabinoids as an antistress mechanism that inhibits elevated adrenomedullary activation and promotes its recovery to baseline in both male and female stressed rats.

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Inhibition of the fatty acid amide hydrolase changes behaviors and brain catecholamines in a sex-specific manner in rats exposed to chronic unpredictable stress

Cited by 22 publications

References 76 publications

Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model

Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model

Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats

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