Voluntary oral consumption of Δ9-tetrahydrocannabinol by adolescent rats impairs reward-predictive cue behaviors in adulthood

Few preclinical approaches are available to study the health impact of voluntary consumption of edibles containing the psychoactive drug Delta(9)-tetrahydrocannabinol (THC). We developed and validated such approach by measuring voluntary oral consumption of THC-containing gelatin by rats and used it to study if and how THC consumption during adolescence impacts adult behavior. We found that adolescent rats of both sexes consumed enough THC to trigger acute hypothermia, analgesic, and locomotor responses, and that 15 days of access to THC-gelatin in adolescence resulted in the down-regulation of cannabinoid 1 receptors (CB(1)Rs) in adulthood in a sex and brain area specific manner. Remarkably, THC consumption by adolescent male rats and not female rats led to impaired Pavlovian reward-predictive cue behaviors in adulthood consistent with a male-specific loss of CB1R-expressing vGlut-1 synaptic terminals in the ventral tegmental area (VTA). Thus, voluntary oral consumption of THC during adolescence is associated with sex-dependent behavioral impairment in adulthood.