Effects of delta 9-tetrahydrocannabinol and cannabidiol on sodium-dependent high affinity choline uptake in the rat hippocampus.

Doses of delta 9-tetrahydrocannabinol (delta 9-THC) and cannabidiol (CBD) affording the same degree of protection against seizures induced by maximal electroshock were compared for their effects on sodium-dependent high affinity choline uptake into six rat brain regions: cortex, striatum, medulla-pons, hypothalamus, midbrain and hippocampus. One hour after administration of CBD, 60 mg/kg i.p. in vitro choline uptake was not altered in any brain region. In contrast, 1 hr after administration of delta 9-THC, 10 mg/kg i.p., in vitro choline uptake in hippocampus and hypothalamus was significantly reduced. Moreover, in vivo administration of delta 9-THC was followed by a dose-related reduction in in vitro hippocampus choline uptake. Kinetic analysis of hippocampal choline uptake after administration of delta 9-THC, 10 mg/kg i.p., indicated that there was a reduction in Vmax with no change in the Km of the transport system. After direct addition to the hippocampal homogenates (in vitro) both delta 9-THC and CBD inhibited choline uptake, with IC50 values of 4.6 and 15.9 microM, respectively. Kinetic analysis revealed that the in vitro choline uptake inhibition induced by delta 9-THC was noncompetitive in nature. These results suggest that the septal-hippocampal cholinergic tract is a major site of action of delta 9-THC and may provide a neurochemical basis for the differential pharmacological properties of delta 9-THC and CBD.