Effect of repeated juvenile exposure to Δ9‑tetrahydrocannabinol on anxiety-related behavior and social interactions in adolescent rats

The gestational and adolescent periods are critically important for brain development and exposure to Δ9‑tetrahydrocannabinol (Δ9-THC) during these periods results in long term behavioral and biochemical abnormalities in laboratory animals. However, recent reports indicate a dramatic rise in oral Δ9-THC exposure in young children but the effects of this exposure scenario have not been adequately investigated. Using a model designed to mimic childhood exposure, male and female rat pups were orally exposed to either corn oil or 10 mg/kg Δ9-THC daily from postnatal days 10-16. On day 29, rats were tested in the elevated plus maze under both low and high illumination with no differences in anxiety-related parameters observed between controls and treated rats. Under high but not low illumination, male Δ9-THC rats exhibited increased anxiolytic behavior as compared to female Δ9-THC rats suggesting a sexual dimorphic effect that was only observed under increased aversiveness. In addition, male Δ9-THC rats had increased activity levels as compared to control males. On day 38, social interactions were determined and both male and female Δ9-THC rats exhibited lower levels of social exploration behaviors but increased episodes of social play behaviors and increased time spent engaged in play. These data suggest that oral exposure to Δ9-THC during a period similar to childhood in humans can result in altered social behavior once adolescence is reached.