Behavioral, proteomic and lipidomic analyses in adult male and female rats exposed to cannabinoids during adolescence: an integrative approach to identify markers of vulnerability for psychiatric disorders and drug abuse

Despite the increasing use of cannabis among adolescents, there are little and often contradictory studies on the long-term neurobiological consequences of cannabis consumption in juveniles. Human studies have some limitations because of the vast heterogeneity of cannabis consumption. Hence, research with laboratory animals offers an important link to gaining further knowledge. We have recently demonstrated that THC administration in adolescent rats produces subtle but lasting alterations in the emotional circuit ending in depressive-like behavior at adulthood. Interestingly, this effect was observed only in females, since male rats do not show behavioral or neurochemical changes that can be associated with a depressive phenotype. This research project is aimed at expanding these data at behavioral and molecular level as well as to investigate whether cannabis exposure during adolescence induces neurobiological modifications responsible for an increased vulnerability to other psychiatric disorders (schizophrenia) and drug abuse in adulthood. Furthermore, a possible difference between males and females will be evaluated. Male and female rats will be treated with increasing doses of THC from post natal day (PND) 35 to 45 and an integrative study including behavioral, neurochemical, morphological, electrophysiological and proteomic approaches will be carried out in adulthood (PND 75). This integrated panel of molecular studies might shed new light on the cellular underpinnings involved in the long-term consequences produced by developmental exposure to cannabinoids and will allow us to expand basic knowledge that can be translated at human level and used to cope with the debated issue of the harmfulness of adolescent cannabis use.