Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite

Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite

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 inhala...

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Bibliographic Details
Published in:Scientific reports Vol. 13; no. 1; p. 22970
Main Authors: Wheeler, Emma C., Choi, Pique, De Howitt, Joanne, Gill, Sumeen, Watson, Shane, Yu, Sue, Wahl, Peyton, Diaz, Cecilia, Mohr, Claudia, Zinski, Amy, Jiang, Zhihua, Rossi, David, Davis, Jon F.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 27-12-2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/378
631/378/1488
631/378/1662
631/443/319/1488
Agouti-Related Protein - metabolism
Animals
Appetite
Cannabinoid receptors
Cannabis
Cannabis - metabolism
Eating - physiology
Electrophysiology
Feeding behavior
Food
Hallucinogens - pharmacology
Humanities and Social Sciences
Hunger
Hypothalamus
Hypothalamus - metabolism
Inhalation
Locomotor activity
Marijuana
Mice
multidisciplinary
Neurons
Neurons - metabolism
Operant conditioning
Rats
Science
Science (multidisciplinary)
Vapors
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Summary: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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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-50112-5