Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels
| Autor: | Karsten Bach, Svenja Ternes, Laura Bindila, Kerstin Michel, Andras Bilkei-Gorzo, Andreas Zimmer, David M. Otte, Beat Lutz, Onder Albayram, Imke Jenniches |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Diacylglycerol lipase biology medicine.medical_treatment Neurogenesis Poison control Anandamide Depolarization-induced suppression of inhibition Endocannabinoid system Open field Developmental psychology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Endocrinology chemistry Internal medicine medicine biology.protein Cannabinoid Psychology 030217 neurology & neurosurgery Biological Psychiatry |
| Zdroj: | Biological Psychiatry. 79:858-868 |
| ISSN: | 0006-3223 |
| Popis: | Background Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB 1 receptors has been linked to depression in humans and depression-like behaviors in mice. The two main endogenous cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), are produced on demand from phospholipids. The pathways and enzymes involved in endocannabinoid biosynthesis thus play a major role in regulating the activity of this system. This study investigates the role of the main 2-AG producing enzyme diacylglycerol lipase α (DAGL-α). Methods We generated and used knockout mice lacking DAGL-α ( Dagla −/− ) to assess the behavioral consequences of reduced endocannabinoid levels in the brain. We performed different behavior tests to determine anxiety- and depression-related behavioral changes in Dagla −/− mice. We also analyzed expression of genes related to the endocannabinoid system via real-time polymerase chain reaction and used the mitotic marker 5-bromo-2′-deoxyuridine to analyze adult neurogenesis. Results Dagla −/− animals show an 80% reduction of brain 2-AG levels but also a reduction in cortical and amygdalar anandamide. The behavioral changes induced by Dagla deletion include a reduced exploration of the central area of the open field, a maternal neglect behavior, a fear extinction deficit, increased behavioral despair, increased anxiety-related behaviors in the light/dark box, and reduced hippocampal neurogenesis. Some of these behavioral changes resemble those observed in animals lacking the CB 1 receptor. Conclusions Our findings demonstrate that the deletion of Dagla adversely affects the emotional state of animals and results in enhanced anxiety, stress, and fear responses. |
| Databáze: | OpenAIRE |
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