Altered Mesolimbic Dopamine System in THC Dependence

To explore the functional consequences of cannabinoid withdrawal in the rat mesolimbic dopamine system, we investigated the anatomical morphology of the mesencephalic, presumed dopaminergic, neurons and their main post-synaptic target in the Nucleus Accumbens. We found that TH-positive neurons shrink and Golgi-stained medium spiny neurons loose dendritic spines in withdrawal rats after chronic cannabinoids administration. Similar results were observed after administration of the cannabinoid antagonist rimonabant to drug-naïve rats supporting a role for endocannabinoids in neurogenesis, axonal growth and synaptogenesis. This evidence supports the tenet that withdrawal from addictive compounds alters functioning of the mesolimbic system. The data add to a growing body of work which indicates a hypodopaminergic state as a distinctive feature of the “addicted brain”.