6533b7dbfe1ef96bd126fe6d
RESEARCH PRODUCT
Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels
Karsten BachKarsten BachSvenja TernesSvenja TernesLaura BindilaKerstin MichelKerstin MichelAndras Bilkei-gorzoAndreas ZimmerDavid M. OtteDavid M. OtteBeat LutzOnder AlbayramOnder AlbayramImke Jennichessubject
0301 basic medicinemedicine.medical_specialtyDiacylglycerol lipasebiologymedicine.medical_treatmentNeurogenesisPoison controlAnandamideDepolarization-induced suppression of inhibitionEndocannabinoid systemOpen fieldDevelopmental psychology03 medical and health scienceschemistry.chemical_compound030104 developmental biology0302 clinical medicineEndocrinologychemistryInternal medicinemedicinebiology.proteinCannabinoidPsychology030217 neurology & neurosurgeryBiological Psychiatrydescription
Abstract 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.
year | journal | country | edition | language |
---|---|---|---|---|
2016-05-01 | Biological Psychiatry |