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Antidepressant-like effects of pharmacological inhibition of FAAH activity in socially isolated female rats
Antidepressant-like effects of pharmacological inhibition of FAAH activity in socially isolated female rats
- Publication Year :
- 2020
-
Abstract
- Pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid N-arachidonoylethanolamine (or anandamide, AEA), exerts favourable effects in rodent models of stress-related depression. Yet although depression seems to be more common among women than men and in spite of some evidence of sex differences in treatment efficacy, preclinical development of FAAH inhibitors for the pharmacotherapy of stress-related depression has been predominantly conducted in male animals. Here, adult female rats were exposed to six weeks of social isolation and, starting from the second week, treated with the FAAH inhibitor URB694 (0.3 mg/kg/day, i.p.) or vehicle. Compared to pair-housed females, socially isolated female rats treated with vehicle developed behavioral (mild anhedonia, passive stress coping) and physiological (reduced body weight gain, elevated plasma corticosterone levels) alterations. Moreover, prolonged social isolation provoked a reduction in brain-derived neurotrophic factor (BDNF) and AEA levels within the hippocampus. Together, these changes are indicative of an increased risk of developing a depressive-like state. Conversely, pharmacological inhibition of FAAH activity with URB694 restored both AEA and BDNF levels within the hippocampus of socially isolated rats and prevented the development of behavioral and physiological alterations. These results suggest a potential interplay between AEA-mediated signaling and hippocampal BDNF in the pathogenesis of depression-relevant behaviors and physiological alterations and antidepressant action of FAAH inhibition in socially isolated female rats.
- Subjects :
- medicine.medical_specialty
Polyunsaturated Alkamides
Hippocampus
Arachidonic Acids
Hippocampal formation
BDNF
Depression
Endocannabinoid
Females
Stress
Amidohydrolases
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Fatty acid amide hydrolase
Neurotrophic factors
Internal medicine
Animals
Medicine
Pharmacology (medical)
Biological Psychiatry
Pharmacology
business.industry
Brain-Derived Neurotrophic Factor
Biphenyl Compounds
Anhedonia
Anandamide
Endocannabinoid system
Antidepressive Agents
Rats
030227 psychiatry
Enzyme Activation
Psychiatry and Mental health
Endocrinology
Social Isolation
nervous system
Neurology
chemistry
Antidepressant
Female
lipids (amino acids, peptides, and proteins)
Carbamates
Neurology (clinical)
medicine.symptom
business
030217 neurology & neurosurgery
Endocannabinoids
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....02c1c43b0a291160a24186b1314aa5bc