| First Author | Jenniches I | Year | 2016 |
| Journal | Biol Psychiatry | Volume | 79 |
| Issue | 10 | Pages | 858-868 |
| PubMed ID | 25981172 | Mgi Jnum | J:250058 |
| Mgi Id | MGI:6102445 | Doi | 10.1016/j.biopsych.2015.03.033 |
| Citation | Jenniches I, et al. (2016) Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels. Biol Psychiatry 79(10):858-868 |
| abstractText | BACKGROUND: Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 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 alpha (DAGL-alpha). METHODS: We generated and used knockout mice lacking DAGL-alpha (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 CB1 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. |
