Protein level alteration of endocannabinoid system components after chronic, oral self-administration of three atypical antipsychotics in rat

DOI: 10.2478/amma-2021-0008

Objective: Atypical antipsychotics (AAPs) often cause metabolic adverse effects (mAE) such as weight gain and dyslipidemia. The mechanisms underlying AAP induced mAE are not fully elucidated. The endocannabinoid system (ECS) is a key system in the regulation of energy metabolism that may be involved in AAPs induced mAE. In this experiment, we studied the expression of three major components of ECS: cannabinoid receptor 1 (CB1), fatty acid amidohydrolase (FAAH) and monoacyl glycerol lipase (MAGL) after chronic administration in rat of three AAPs: olanzapine (Ola), aripiprazole (Ari) and cariprazine (Car).
Methods: Drugs were self-administered orally, in two doses by female, adult Wistar white rats (n=6 per treatment group) for six weeks. After the treatment period, the animals were sacrificed and visceral (perirenal) white fat pads were collected. The fat tissue samples were homogenized and the expression level of CB1, FAAH and MAGL were compared by western-blot analysis.
Results: An increase of CB1 expression was noticed after the treatment with 1.5 mg/kg/day Ola, although not statistically significant. All three drugs augmented the FAAH expression, the effect being significant after the treatment with 0.25 mg/kg/day Car. The expression of MAGL was not influenced significantly by the three AAPs, nevertheless, an increasing tendency can be remarked in the case of Ari and Car.
Conclusions: Promoting the CB1 expression in adipose tissue could contribute to weight increasing and other mAE effects of Ola. The tendency of Ari and Car to enhance the breakdown enzymes expression might have some role in more favorable mAE of these drugs.

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