RATIONALE: Recent evidence suggests that in addition to controlling emotional behavior
in general, endocannabinoid signaling is engaged in shaping behavioral responses to
challenges. This important function of endocannabinoids is still poorly understood.
OBJECTIVES: Here we investigated the impact of blockade of fatty acid amide hydrolase
(FAAH), the degrading enzyme of anandamide on behavioral responses induced by challenges
of different intensity. METHODS: Mice treated with FAAH inhibitor URB597 were either
manually restrained on their backs (back test) or received foot-shocks. RESULTS: The
behavior of mice showed bimodal distribution in the back test: they either predominantly
showed escape attempts or equally distributed time between passivity and escape. URB597
increased escapes in animals with low escape scores. No effects were noticed in mice
showing high escape scores, which is likely due to a ceiling effect. We hypothesized
that stronger stressors would wash out individual differences in coping; therefore,
we exposed mice to foot-shocks that decreased locomotion and increased freezing in
all mice. URB597 ameliorated both responses. The re-exposure of mice to the shock
cage 14 days later without delivering shocks or treatment was followed by reduced
and fragmented sleep as shown by electrophysiological recordings. Surprisingly, sleep
was more disturbed after the reminder than after shocks in rats receiving vehicle
before foot-shocks. These reminder-induced disturbances were abolished by URB597 administered
before shocks. CONCLUSIONS: These findings suggest that FAAH blockade has an important
role in the selection of behavioral responses under challenging conditions and-judging
from its long-term effects-that it influences the cognitive appraisal of the challenge.
