Frequent Low-Dose Δ
During adolescence, microglia are actively involved in neocortical maturation while concomitantly undergoing profound phenotypic changes. Because the teenage years are also a time of experimentation with cannabis, we evaluated whether adolescent exposure to the drugs psychotropic constituent, Δ We administered THC (5 mgkg, intraperitoneal) once daily to male and female mice from postnatal day (PND) 30 to PND44 and examined the transcriptome of purified microglia in adult animals (PND70 and PND120) under baseline conditions or following either of two interventions known to recruit microglia lipopolysaccharide injection and repeated social defeat. We used high-dimensional mass cytometry by time-of-flight to map brain immune cell populations after lipopolysaccharide challenge. Adolescent THC exposure produced in mice of both sexes a state of microglial dyshomeostasis that persisted until young adulthood (PND70) but receded with further aging (PND120). Key features of this state included broad alterations in genes involved in microglia homeostasis and innate immunity along with marked impairments in the responses to lipopolysaccharide- and repeated social defeat-induced psychosocial stress. The endocannabinoid system was also dysfunctional. The effects of THC were prevented by coadministration of either a global CB Daily low-intensity CB