Temporal changes in N-acylethanolamine content and metabolism throughout the peri-adolescent period

Fatty acid amide hydrolase (FAAH) regulates tissue concentrations of N-acylethanolamines (NAEs), including the endocannabinoid, N-arachidonylethanolamide (anandamide, AEA). FAAH activity and NAEs are widely distributed throughout the brain and FAAH activity regulates an array of processes including emotion, cognition, inflammation, and feeding. However, there is relatively little research describing how this system develops throughout adolescence, particularly within limbic circuits regulating stress and reward processing. Thus, this study characterized temporal changes in NAE content (AEA, oleoylethanolamine [OEA], and palmitoylethanolamide [PEA]) and FAAH activity across the peri-adolescent period, in four corticolimbic structures (amygdala, hippocampus, prefrontal cortex, and hypothalamus). Brain tissue of male Sprague-Dawley rats was collected on postnatal days (PND) 25, 35, 45, and 70, representing pre-adolescence, early- to mid-adolescence, late adolescence, and adulthood, respectively. Tissue was analyzed for AEA, OEA, and PEA content as well as FAAH activity at each time point. AEA, OEA, and PEA exhibited a similar temporal pattern in all four brain regions. NAE concentrations were lowest at PND 25 and highest at PND 35. NAE concentrations decreased between PNDs 35 and 45 and increased between PNDs 45 and 70. FAAH activity mirrored the pattern of NAE content in which it decreased between PNDs 25 and 35, increased between PNDs 35 and 45, and decreased between PNDs 45 and 70. These age-dependent patterns of NAE content and FAAH activity demonstrate temporal specificity to the development of this system and could contribute to alterations in stress sensitivity, emotionality, and executive function which also fluctuate during this developmental period.