Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety
| Autor: | Andrew D. Gaulden, Nolan D. Hartley, Md. Jashim Uddin, Toni A. Patrick, Emily Neale, Philip J. Kingsley, Gaurav Bedse, Niels Plath, Lawrence J. Marnett, Sachin Patel |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Polyunsaturated Alkamides Pyridines medicine.drug_class 2-Arachidonoylglycerol Arachidonic Acids Anxiety Amygdala Anxiolytic Article Glycerides Developmental psychology Heterocyclic Compounds 1-Ring Mice 03 medical and health sciences chemistry.chemical_compound Glutamatergic 0302 clinical medicine Piperidines medicine Animals Benzodioxoles Dronabinol Biological Psychiatry JZL184 Cannabinoid Receptor Agonists Mice Inbred ICR Adaptation Ocular Brain Excitatory Postsynaptic Potentials Anandamide Cyclohexanols Endocannabinoid system 030227 psychiatry Disease Models Animal medicine.anatomical_structure Anti-Anxiety Agents chemistry lipids (amino acids peptides and proteins) medicine.symptom Psychology Neuroscience Locomotion 030217 neurology & neurosurgery Endocannabinoids Signal Transduction |
| Zdroj: | Biological Psychiatry. 82:488-499 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2017.03.002 |
| Popis: | Background Increasing the available repertoire of effective treatments for mood and anxiety disorders represents a critical unmet need. Pharmacological augmentation of endogenous cannabinoid (eCB) signaling has been suggested to represent a novel approach to the treatment of anxiety disorders; however, the functional interactions between two canonical eCB pathways mediated via anandamide (N-arachidonylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG) in the regulation of anxiety are not well understood. Methods We utilized pharmacological augmentation and depletion combined with behavioral and electrophysiological approaches to probe the role of 2-AG signaling in the modulation of stress-induced anxiety and the functional redundancy between AEA and 2-AG signaling in the modulation of anxiety-like behaviors in mice. Results Selective 2-AG augmentation reduced anxiety in the light/dark box assay and prevented stress-induced increases in anxiety associated with limbic AEA deficiency. In contrast, acute 2-AG depletion increased anxiety-like behaviors, which was normalized by selective pharmacological augmentation of AEA signaling and via direct cannabinoid receptor 1 stimulation with Δ9-tetrahydrocannabinol. Electrophysiological studies revealed 2-AG modulation of amygdala glutamatergic transmission as a key synaptic correlate of the anxiolytic effects of 2-AG augmentation. Conclusions Although AEA and 2-AG likely subserve distinct physiological roles, a pharmacological and functional redundancy between these canonical eCB signaling pathways exists in the modulation of anxiety-like behaviors. These data support development of eCB-based treatment approaches for mood and anxiety disorders and suggest a potentially wider therapeutic overlap between AEA and 2-AG augmentation approaches than was previously appreciated. |
| Databáze: | OpenAIRE |
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