Conditioned gaping produced by high dose Δ9-tetrahydracannabinol: Dysregulation of the hypothalamic endocannabinoid system
| Autor: | Erin M. Rock, Lauren Sabaziotis, Kelly M. Hrelja, Cheryl L. Limebeer, David M. Mutch, Alex Rajna, Linda A. Parker, Marieka V. DeVuono |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cannabinoid receptor medicine.medical_treatment 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Rimonabant Internal medicine mental disorders medicine Pharmacology Chemistry organic chemicals Antagonist Endocannabinoid system 3. Good health Monoacylglycerol lipase 030104 developmental biology Endocrinology Hypothalamus Vomiting Cannabinoid medicine.symptom 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropharmacology. 141:272-282 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2018.08.039 |
| Popis: | Δ9-tetrahydracannabinol (THC) is recognized as an effective treatment for nausea and vomiting via its action on the cannabinoid 1 (CB1) receptor. Paradoxically, there is evidence that THC can also produce nausea and vomiting. Using the conditioned gaping model of nausea in rats, we evaluated the ability of several doses of THC (0.0, 0.5, 5 and 10 mg/kg, i.p.) to produced conditioned gaping reactions. We then investigated the ability of the CB1 receptor antagonist, rimonabant, to block the establishment of THC-induced conditioned gaping. Real-time polymerase chain reaction (RT-PCR) was then used to investigate changes in endocannabinoid related genes in various brain regions in rats chronically treated with vehicle (VEH), 0.5 or 10 mg/kg THC. THC produced dose-dependent gaping, with 5 and 10 mg/kg producing significantly more gaping reactions than VEH or 0.5 mg/kg THC, a dose known to have anti-emetic properties. Pre-treatment with rimonabant reversed this effect, indicating that THC-induced conditioned gaping was CB1 receptor mediated. The RT-PCR analysis revealed an upregulation of genes for the degrading enzyme, monoacylglycerol lipase (MAGL), of the endocannabinoid, 2-arachidolyl glycerol (2-AG), in the hypothalamus of rats treated with 10 mg/kg THC. No changes in the expression of relevant genes were found in nausea (interoceptive insular cortex) or vomiting (dorsal vagal complex) related brain regions. These findings support the hypothesis that THC-induced nausea is a result of a dysregulated hypothalamic-pituitary-adrenal axis leading to an overactive stress response. |
| Databáze: | OpenAIRE |
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