FIG. 3.

FAAH inhibition restores fluoxetine sensitivity in the FST following THC or CBD-PCE. (A) FAAH inhibition by 0.3 mg/kg, but not 0.1 mg/kg nor 1 mg/kg of URB597 significantly reduces immobility time in the FST. (B) URB597 treatment (0.1 mg/kg) did not affect FST-immobility time for any PCE treatment (p>0.999 for all). Following URB597 pretreatment, fluoxetine robustly decreased immobility times in mice receiving PCE with either THC or CBD. URB597 treatment did not significantly affect decreased immobility following PCE with either vehicle or THC+CBD. Bar graphs are presented as mean±SEM. Statistical interactions were first assessed by three-way ANOVA. PCE and treatment, but not gender, were identified as major sources of variation. Two-way ANOVA was then conducted with males and females combined. This identified fluoxetine (F (1, 109)=87.36; p<0.0001) as the source of variation, with no interaction between fluoxetine and PCE (F (3, 109)=0.7046; p=0.5513). Bonferroni test was used for multiple comparisons. *p<0.05, ***p<0.001, ****p<0.0001. FAAH, fatty acid amide hydrolase; URB, URB597. Color images are available online.