2007; Ohno-Shosaku, et al 2002) and CB1 receptor expression is significantly lower on glutamatergic terminals than GABA axon terminals in the hippocampus (Katona, et al 2006; Kawamura, et al 2006). Moreover, chronic exposure to Δ9-THC in vitro results in tolerance to the inhibitory effects of the cannabinoid agonist WIN, 212-2 but does not affect glutamate release in the hippocampus (Hoffman, et al 2007). Of importance, both Δ9-THC and CP-55,940 decreased the power of theta, gamma, and ripple oscillations in the hippocampus of rats that correlated with memory impairment in the delayed alternation memory paradigm, a hippocampus-dependent task (Robbe, et al 2006). Finally, the GABAA antagonist, bicucculine, blocked Δ9-THC-induced memory deficits in a mouse Morris water maze task (Varvel, et al 2004b). Taken together, these findings are consistent with the notion that CB1 receptors located on inhibitory axon terminals may be the primary target of Δ9-THC in the hippocampus.
