The cannabinoid 1-receptor silent antagonist O-2050 attenuates preference for high-fat diet and activated astrocytes in mice
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Updated: Jun 16, 2026

Oromucosal as an Alternative Method for Administration of Cannabis Products in Rodents
Published on: August 22, 2025
Sei Higuchi1, Keiichi Irie, Shohei Mishima
1Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Abstract:
Endocannabinoids have been shown to activate reward-related feeding and to promote astrocytic differentiation. We investigated whether high-fat diet (HFD) intake produced a preference for HFD via an endocannabinoid-dependent mechanism. In the conditioned place preference test, the 2-week HFD-intake group showed preference for HFD and had increased expression of a marker for reactive astrocytes, glial fibrillary acid protein (GFAP), in the hypothalamus. The cannabinoid CB(1)-receptor antagonist O-2050 reduced the preference for HFD and expression of GFAP in the hypothalamus. These results suggested that HFD intake led to the development of a preference for HFD via astrocytic CB(1) receptors in the hypothalamus.
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