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Publication : Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite.

First Author  Wheeler EC Year  2023
Journal  Sci Rep Volume  13
Issue  1 Pages  22970
PubMed ID  38151493 Mgi Jnum  J:343758
Mgi Id  MGI:7569901 Doi  10.1038/s41598-023-50112-5
Citation  Wheeler EC, et al. (2023) Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite. Sci Rep 13(1):22970
abstractText  The neurobiological mechanisms that regulate the appetite-stimulatory properties of cannabis sativa are unresolved. This work examined the hypothesis that cannabinoid-1 receptor (CB1R) expressing neurons in the mediobasal hypothalamus (MBH) regulate increased appetite following cannabis vapor inhalation. Here we utilized a paradigm where vaporized cannabis plant matter was administered passively to rodents. Initial studies in rats characterized meal patterns and operant responding for palatable food following exposure to air or vapor cannabis. Studies conducted in mice used a combination of in vivo optical imaging, electrophysiology and chemogenetic manipulations to determine the importance of MBH neurons for cannabis-induced feeding behavior. Our data indicate that cannabis vapor increased meal frequency and food seeking behavior without altering locomotor activity. Importantly, we observed augmented MBH activity within distinct neuronal populations when mice anticipated or consumed food. Mechanistic experiments demonstrated that pharmacological activation of CB1R attenuated inhibitory synaptic tone onto hunger promoting Agouti Related Peptide (AgRP) neurons within the MBH. Lastly, chemogenetic inhibition of AgRP neurons attenuated the appetite promoting effects of cannabis vapor. Based on these results, we conclude that MBH neurons contribute to the appetite stimulatory properties of inhaled cannabis.
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