RATIONALE: Several lines of recent evidence suggest that endocannabinoids affect behavior
by influencing the general patterns of challenge responding. OBJECTIVES: Here, we
investigated the brain mechanisms underlying this phenomenon in rats. METHODS: The
anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel
cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL)
or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid
action. Thereafter, we investigated behavioral responsiveness to ambient light level
in the elevated plus-maze and conditioned fear tests. RESULTS: URB597 concentration
was ~30 mug/mg protein in target areas; local brain anandamide levels increased threefold,
without significant changes in 2-arachidonoylglycerol. High levels of illumination
halved the time spent by controls in the open arms of the plus-maze. No similar decrease
was observed in rats with URB597 implants in the PRL. High light decreased conditioned
fear by 30 % in controls, but not in rats with prelimbic URB597 implants. Unresponsiveness
to environmental challenges was not attributable to the anxiolytic effects of anandamide
enhancement, as implants induced paradoxical anxiogenic-like effects under low light,
which could be explained by effects on stimulus responsiveness rather than by effects
on anxiety. URB597 implants targeting the BLA did not affect stimulus responsiveness.
CONCLUSIONS: Our findings show that elevated prelimbic anandamide signaling leads
to less environment-dependent (more autonomous) behavioral responses to challenges,
which is an attribute of active coping styles. These findings are discussed in light
of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis"
and "active coping."
