That repeated restraint stress and MAFP produce mutually occlusive prolongation of DSI suggests decreased 2-AG degradation may contribute to this effect. However, earlier studies showed no changes in MGL activity in response to 10 days of restraint stress (Rademacher et al, 2008), and we have not detected changes in MGL protein expression after 10 days of restraint stress (Patel and Winder, unpublished data). MGL contributes approximately 85% of the 2-AG hydrolytic activity in mouse brain, however, two other enzymes ABHD6 and ABHD12 contribute approximately 4 and 12%, respectively (Blankman et al, 2007). It has been suggested that ABHD12 may preferentially be involved in the regulation of synaptically available 2-AG based on its extracellular hydrolytic activity (Blankman et al, 2007). The possibility that repeated restraint stress modulates the duration of 2-AG signaling through alterations ABDH12 rather than MGL remains to be tested.
