GABAergic mediation in the inhibition of hippocampal acetylcholine turnover rate elicited by delta 9-tetrahydrocannabinol.

Both intravenous Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and intraseptal muscimol reduce the turnover rate of acetylcholine (TR_ACh) in the hippocampus by 50 and 58%, respectively, without affecting the hippocampal content of ACh. The ACh content and the TR_ACh, in other areas of rat brain examined are unchanged. Bicuculline fails to alter the hippocampal TR_ACh when administered intraseptally but prevents the decreased hippocampal TR_ACh induced by Δ⁹-THC or muscimol. The effect is specific to the septal-hippocampal cholinergic pathway since lesioning the fimbria (2 hr) abolishes the effect. Moreover, neither naltrexone nor destruction of septal dopaminergic nerve terminals with 6-hydroxy-dopamine injected into area A₁₀ prevents the decreased TR_ACh after Δ⁹-THC. This suggests that neither endophinergic nor dopaminergic neurons are involved in the reduction of the TR_ACh in the hippocampas following administration of Δ⁹-THC or muscimol. When the metabolism of γ-aminobutyric acid (TR_GABA) is measured, Δ⁹-THC produces a 2-fold increase in the TR_GABA which is specific for the septum. These results suggest that Δ⁹-THC inhibits TR_ACh in the cholinergic septal-hippocampal pathway by increasing the release of GABA from septal GABAergic interneurons.