Δ⁹-Tetrahydrocannabinol alters cerebral metabolism in a biphasic, dose-dependent mannier in rat brain

Δ⁹-tetrahydrocannabinol (THC)-induced alterations in limbic and neocortical function are associated with deficiencies in short-term memory and recall. The 2-deoxy-D-glucose (2DG) autoradiographic method was used to examine the effect of acute THC administration (0, 0.2, 0.5, 2.0, 10.0 mg/kg) on regional brain metabolism in limbic and cortical brain regions of male rats. THC altered 2DG uptake in a biphasic, dose-dependent manner in most limbic and cortical structures, however most diencephalic and brainstem structures examined were unaffected. The 0.2 mg/kg THC dose significantly increased 2DG uptake relative to vehicle treatment in ail cortical and selected limbic regions, whereas the 2.0 and 10.0 mg/kg THC doses decreased 2DG uptake in most of these regions. Certain limbic regions, particularly the hippocampus, are more sensitive to THC suggesting a selective regional action of the drug at lower doses. The incidence of enhanced metabolic activity in limbic and cortical regions is consistent with the occurrence of high density cannabinoid receptors in these regions.