At the in vivo level, the first study to examine the effects of stress on endocannabinoid signaling was performed in the laboratory of Cecilia Hillard, in which, contrary to expectations, acute stress to mice was found to result in a reduction in 2-AG content within the hypothalamus without affecting the tissue levels of AEA (Patel et al., 2004). Examination of the effects of acute restraint stress on other brain structures revealed that there was no effect of acute stress on endocannabinoid ligand content in the forebrain or cerebellum, and within the amygdala stress resulted in a reduction AEA content without affecting 2-AG levels (Patel et al., 2005). Subsequent studies from this same group examining the effects of a common acute restraint stress on endocannabinoid content in the mouse found similar results in that stress did not modulate endocannabinoid content in the medial prefrontal cortex (PFC) or ventral striatum, but again produced a reduction in amygdalar AEA content without affecting 2-AG (Rademacher et al., 2008). As such, these studies were not very consistent with the in vitro work performed by Tasker and colleagues.
