Cannabis use has been frequently associated with sex-dependent effects on brain 
and behavior. We previously demonstrated that adult female rats exposed to 
delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term 
alterations in cognitive performances and emotional reactivity, whereas 
preliminary evidence suggests the presence of a different phenotype in male 
rats. To thoroughly depict the behavioral phenotype induced by adolescent THC 
exposure in male rats, we treated adolescent animals with increasing doses of 
THC twice a day (PND 35-45) and, at adulthood, we performed a battery of 
behavioral tests to measure affective- and psychotic-like symptoms as well as 
cognition. Poorer memory performance and psychotic-like behaviors were present 
after adolescent THC treatment in male rats, without alterations in the 
emotional component. At cellular level, the expression of the NMDA receptor 
subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, 
were significantly increased in hippocampal post-synaptic fractions from 
THC-exposed rats compared to controls. Furthermore, increases in the levels of 
the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, 
were also present. Interestingly, KCl-induced [(3)H]D-ASP release from 
hippocampal synaptosomes, but not gliosomes, was significantly enhanced in 
THC-treated rats compared to controls. Moreover, in the same brain region, 
adolescent THC treatment also resulted in a persistent neuroinflammatory state, 
characterized by increased expression of the astrocyte marker, GFAP, increased 
levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a 
concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of 
these alterations was observed in the prefrontal cortex (PFC). Together with our 
previous findings in females, these data suggest that the sex-dependent 
detrimental effects induced by adolescent THC exposure on adult behavior may 
rely on its ability to trigger different region-dependent changes in glutamate 
synapse and glial cells. The phenotype observed in males is mainly associated 
with marked dysregulations in the hippocampus, whereas the prevalence of 
alterations in the emotional sphere in females is associated with profound 
changes in the PFC.