Cannabidiol induces antidepressant and anxiolytic‐like effects in experimental type-1 diabetic animals by multiple sites of action
Autor: | Joice Maria da Cunha, Karina Genaro, José Alexandre de Souza Crippa, Janaina Menezes Zanoveli, Yane Costa Chaves |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
AM251 Male Elevated plus maze medicine.drug_class Pharmacology Biochemistry Diabetes Mellitus Experimental 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Receptor Cannabinoid CB1 medicine Animals Cannabidiol Rats Wistar Receptor Maze Learning 5-HT receptor business.industry Antagonist Receptor antagonist Antidepressive Agents Rats 030104 developmental biology Diabetes Mellitus Type 1 Anti-Anxiety Agents Receptor Serotonin 5-HT1A Antidepressant lipids (amino acids peptides and proteins) Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug SEROTONINA |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
Popis: | Cannabidiol (CBD), a phytocannabinoid compound, presents antidepressant and anxiolytic-like effects in the type-1 diabetes mellitus(DM1) animal model. Although the underlying mechanism remains unknown, the type-1A serotonin receptor (5-HT1A) and cannabinoids type-1 (CB1) and type-2 (CB2) receptors seem to play a central role in mediating the beneficial effects on emotional responses. We aimed to study the involvement of these receptors on an antidepressant- and anxiolytic-like effects of CBD and on some parameters of the diabetic condition itself. After 2 weeks of the DM1 induction in male Wistar rats by streptozotocin (60 mg/kg; i.p.), animals were treated continuously for 2-weeks with the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg, i.p.), CB1 antagonist AM251 (1 mg/kg i.p.) or CB2 antagonist AM630 (1 mg/kg i.p.) before the injection of CBD (30 mg/kg, i.p.) or vehicle (VEH, i.p.) and then, they were submitted to the elevated plus-maze and forced swimming tests. Our findings show the continuous treatment with CBD improved all parameters evaluated in these diabetic animals. The previous treatment with the antagonists − 5-HT1A, CB1, or CB2 - blocked the CBD-induced antidepressant-like effect whereas only the blockade of 5-HT1A or CB1 receptors was able to inhibit the CBD-induced anxiolytic-like effect. Regarding glycemic control, only the blockade of CB2 was able to inhibit the beneficial effect of CBD in reducing the glycemia of diabetic animals. These findings indicated a therapeutic potential for CBD in the treatment of depression/anxiety associated with diabetes pointing out a complex intrinsic mechanism in which 5-HT1A, CB1, and/or CB2 receptors are differently recruited. |
Databáze: | OpenAIRE |
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