Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice

Abstract

Heavy and daily use of cannabis with high contents of Δ⁹-tetrahydrocannabinol (THC) during adolescence is associated with an increased risk of developing psychotic disorders later in life. Here, we treated mice with THC during adolescence and found that this exposure impaired social interaction and increased vulnerability to develop sensorimotor gating deficiencies comparable to those previously described among heavy cannabis consumers. Importantly, we provide evidence on long-term cortico-striatal dysconnectivity induced by exposure to THC during adolescence and its correlation with impaired social interactions occurring later in adulthood. Moreover, we have observed long-lasting molecular alterations in key elements that regulate the mesolimbic dopaminergic system, namely on the balance between dopamine D₂, adenosine A_2A, and cannabinoid CB₁ receptors in the striatum of treated mice. Together, these findings contribute to a better understanding of the neurobiological bases of the deleterious effects associated with cannabis abuse during adolescence.