While direct administration of cannabinoids into the hippocampus reliably impairs spatial memory (Egashira, et al 2002; Lichtman, et al 1995; Mishima, et al 2001; Wegener, et al 2008), it is unclear whether hippocampal CB1 receptors play a critical role in the memory disruptive effects of systemically administered cannabinoids. Thus, the primary objective of the present study was to determine whether intrahippocampal administration of the selective CB1 receptor antagonist, rimonabant, would prevent the memory disruptive effects of systemically administered Δ9-THC or CP-55,940 in the radial arm maze, a well established hippocampus-dependent spatial memory task (Olton 1987) that is sensitive to the memory disruptive effects of cannabinoids (Lichtman, et al 1995; Lichtman and Martin 1996; Nakamura, et al 1991). In an initial experiment, we established the dose of rimonabant that would block the memory disruptive effects of CP-55,940, when both drugs were infused bilaterally into the hippocampus. Subsequent studies evaluated whether intrahippocampal administration of the active rimonabant dose would block the memory disruptive effects of systemically administered cannabinoids. To control for the possibility that rimonabant elicited its effects because of diffusion to
