The results of the present study indicate that CB1 receptors in the hippocampus play a necessary role in Δ9-THC-induced memory impairment; however, it is unclear which specific hippocampal neurons mediated these memory impairing effects. CB1 receptors are predominantly localized on the terminals of a subset of GABAergic basket cell interneurons (Marsicano and Lutz 1999); however, they have also been demonstrated to inhibit glutamatergic transmission in cultured hippocampal cells (Shen, et al 1996). Overall, the evidence favors a predominant role for GABAergic pathways in the memory disruptive effects of cannabinoids. Specifically, activation of hippocampal CB1 receptors decreases GABA release (Hajos, et al 2000; Hoffman and Lupica 2000; Hoffman, et al 2003; Katona, et al 1999). CB1 receptors located on GABAergic axon terminals are activated by lower concentrations of cannabinoid receptor agonists than CB1 receptors located on glutamatergic terminals (Hoffman, et al 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
