Ultrastructural and Immunohistochemical Changes of Rat Brain after Long-Term Marijuana Inhalation

Ultrastructural changes of the brain of rats that inhaled marijuana cigarettes for 8 weeks were examined by electron microscopy, simultaneously with immunohistochemical investigation for serotonergic neuronal activities in the nucleus accumbens (NAc), the hippocampus (CA-1) and the nucleus raphe dorsalis (NRD). In the animals that inhaled marijuana, numerous cored and coated vesicles were observed near the well-developed Golgi apparatus of the NRD neurons. The lamellar membranous structure was found frequently in the dendrite, and occasionally in the axon, and the synapse of the marijuana-smoking animals. The serotonin-immunostainability in neurons of the NRD was significantly stronger in the animals that inhaled marijuana than in the non-treated ones. The serotonin-immunostainability in nerve fibers and terminals of the NAc and the CA-1 showed an obvious decrease compared with that of the non-treated animals. These findings suggest that the neurons in the NRD that is the original nucleus of the serotonergic nerve system have become functionally hyperactive by Δ9-tetrahydrocannabinol, but it may induce the dysfunction of serotonin transmission from the original nucleus.