@article{ref1,
title="Anxiety, stress, and fear response in mice with reduced endocannabinoid levels",
journal="Biological psychiatry",
year="2015",
author="Jenniches, Imke and Ternes, Svenja and Albayram, Onder and Otte, David M. and Bach, Karsten and Bindila, Laura and Michel, Kerstin and Lutz, Beat and Bilkei-Gorzo, Andras and Zimmer, Andreas",
volume="79",
number="10",
pages="858-868",
abstract="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 α (DAGL-α). <br><br>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. <br><br>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. <br><br>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.<p /> <p>Language: en</p>",
language="en",
issn="0006-3223",
doi="10.1016/j.biopsych.2015.03.033",
url="http://dx.doi.org/10.1016/j.biopsych.2015.03.033"
}