Cannabinoids Activate Monoaminergic Signaling to Modulate Key C. elegans Behaviors
| Autor: | Bruce A. Bamber, Richard Komuniecki, Tobias Clark, Mitchell Oakes, Wen Jing Law |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nociception Cannabinoid receptor medicine.medical_treatment Biology Serotonergic Synaptic Transmission Animals Genetically Modified 03 medical and health sciences chemistry.chemical_compound Monoaminergic Cannabinoid receptor type 2 medicine Avoidance Learning Animals Biogenic Monoamines Receptor Caenorhabditis elegans Research Articles Neurotransmitter Agents Behavior Animal Cannabinoids General Neuroscience digestive oral and skin physiology Anandamide Feeding Behavior 030104 developmental biology chemistry GPR18 lipids (amino acids peptides and proteins) Cannabinoid Neuroscience Endocannabinoids |
| Popis: | Cannabis sativa, or marijuana, a popular recreational drug, alters sensory perception and exerts a range of potential medicinal benefits. The present study demonstrates that the endogenous cannabinoid receptor agonists 2-arachidonoylglycerol (2-AG) and anandamide (AEA) activate a canonical cannabinoid receptor inCaenorhabditis elegansand also modulate monoaminergic signaling at multiple levels. 2-AG or AEA inhibit nociception and feeding through a pathway requiring the cannabinoid-like receptor NPR-19. 2-AG or AEA activate NPR-19 directly and cannabinoid-dependent inhibition can be rescued innpr-19-null animals by the expression of a human cannabinoid receptor, CB1, highlighting the orthology of the receptors. Cannabinoids also modulate nociception and locomotion through an NPR-19-independent pathway requiring an α2A-adrenergic-like octopamine (OA) receptor, OCTR-1, and a 5-HT1A-like serotonin (5-HT) receptor, SER-4, that involves a complex interaction among cannabinoid, octopaminergic, and serotonergic signaling. 2-AG activates OCTR-1 directly. In contrast, 2-AG does not activate SER-4 directly, but appears to enhance SER-4-dependent serotonergic signaling by increasing endogenous 5-HT. This study defines a conserved cannabinoid signaling system inC. elegans, demonstrates the cannabinoid-dependent activation of monoaminergic signaling, and highlights the advantages of studying cannabinoid signaling in a genetically tractable whole-animal model.SIGNIFICANCE STATEMENTCannabis sativa, or marijuana, causes euphoria and exerts a wide range of medicinal benefits. For years, cannabinoids have been studied at the cellular level using tissue explants with conflicting results. To better understand cannabinoid signaling, we have used theCaenorhabditis elegansmodel to examine the effects of cannabinoids on behavior. The present study demonstrates that mammalian cannabinoid receptor ligands activate a conserved cannabinoid signaling system inC. elegansand also modulate monoaminergic signaling, potentially affecting an array of disorders, including anxiety and depression. This study highlights the potential role of cannabinoids in modulating monoaminergic signaling and the advantages of studying cannabinoid signaling in a genetically tractable, whole-animal model. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|