Enhanced anandamide signaling reduces flight behavior elicited by an approaching robo-beetle

• Published in: Neuropharmacology 2017-11, Vol.126, p.233-241
• Main Authors: Heinz, Daniel E., Genewsky, Andreas, Wotjak, Carsten T.
• Format: Article
• Language: English
• Subjects: 2-AG; Active-fear; Amidohydrolases - antagonists & inhibitors; Anandamide; Animals; Anti-Anxiety Agents - administration & dosage; Anxiety - physiopathology; Arachidonic Acids - physiology; Avoidance Learning - drug effects; Avoidance Learning - physiology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Benzamides - administration & dosage; Benzodioxoles - administration & dosage; Cannabinoid Receptor Agonists - administration & dosage; Carbamates - administration & dosage; Diazepam - administration & dosage; Endocannabinoids - physiology; Fear - drug effects; Fear - physiology; Inbred mice; JZL184; Male; Mice, Inbred C57BL; Monoacylglycerol Lipases - antagonists & inhibitors; Panic; Piperidines - administration & dosage; Polyunsaturated Alkamides; Pyrazoles - administration & dosage; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Robo-beetle; URB597
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2017.09.010

Our current knowledge of the implications of endocannabinoids in fear and anxiety is largely based on fear conditioning paradigms and approach-avoidance conflicts. Here we establish the ethobehavioral beetle mania task (BMT), which confronts mice with an erratically moving robo-beetle. With the help of this task we demonstrate decreased tolerance yet increased avoidance responses to an approaching beetle in high-anxiety behavior (HAB) and BALBc mice compared to C57BL/6N, CD1 and normal-anxiety behavior (NAB) mice. Also DBA/2N mice showed decreased passive and increased active behavior, but followed the robo-beetle more often than HAB and BALBc mice. Treatment with diazepam (1 mg/kg) increased tolerance without affecting avoidance behavior in HAB mice. Treatment with the MAGL inhibitor JZL184 (8 mg/kg) increased flight behavior, but did not affect tolerance. The FAAH inhibitor URB597 (0.3 mg/kg), however, reduced flight behavior and enhanced tolerance to the robo-beetle. The latter effects were blocked by co-treatment with the CB1 receptor antagonist SR141716A (3 mg/kg), which failed to affect the behavior by itself. Taken together, we validate the BMT as a novel test for studying endocannabinoids beyond traditional paradigms and for assessing active fear responses in mice. Furthermore, we demonstrate panicolytic consequences of pharmacological enhancement of anandamide, but not 2-AG signaling. •The new beetle mania task (BMT) allows the assessment of passive and active fear responses in mice.•High-anxiety behavior (HAB) and BALBc mice show exaggerated active fear.•MAGL inhibitor JZL184 increases flight behavior in HAB mice.•FAAH inhibitor URB597 exerts panicolytic effects in both HAB and BALBc mice.•The effects of URB597 depend on CB1 receptors.