Determining impacts of prenatal cannabis exposure on cannabis vapor self-administration using a novel response-contingent vapor model in pregnant rat dams

Cannabis use during pregnancy is becoming increasingly common despite a lack of knowledge regarding its long-term effects on developing offspring. Determining effects of prenatal cannabis exposure on cannabis use later in life has been especially difficult given the problems inherent to traditional models of cannabinoid self-administration. Thus, we adopted a model of response-contingent cannabis vapor delivery in pregnant rat dams to investigate impacts of maternal cannabis use on reinforcing properties of ∆⁹-tetrahydrocannabinol (THC)-rich cannabis vapor in offspring. Rat dams were trained to self-administer a vaporized cannabis extract or vehicle vapor in 1-hr sessions twice daily until 24-48 hr prior to parturition, while a third group received no vapor exposure. Cannabis vapor self-administration was assessed in adult offspring using a 22-day escalating reinforcement schedule that culminated in a 3 hr progressive ratio challenge. Dams reliably self-administered cannabis vapor during the gestational period and showed better discrimination for the vapor-paired nosepoke than vehicle self-administering dams. In accordance with human data, cannabis-exposed offspring displayed lower birthweights than vehicle-exposed offspring. Effects of prenatal cannabis exposure on vapor self-administration in adult offspring differed by sex. Male cannabis-exposed offspring made fewer active responses and earned fewer vapor deliveries than vehicle-exposed offspring, regardless of their assigned vapor condition. Conversely, female offspring showed higher rates of responding for cannabis relative to vehicle, but rates of self-administration were unaffected by prenatal cannabis exposure. Altogether, these data demonstrate feasibility of response-contingent cannabis vapor delivery in pregnant rat dams and indicate paradoxical suppressive effects on vapor self-administration in male offspring.