In previous studies, we demonstrated the disruptive effects on spatial working memory of the major psychoactive component of cannabis, Δ9-tetrahydrocannabinol
(Δ9-THC), following both systemic administration and local injection into the medial PFC (mPFC) (Nakamura et al., 1991 and Silva de Melo et al., 2005). The impairing effects of CB1 receptor ligand Δ9-THC, the endogenous CB1 receptor agonist anandamide and synthetic cannabinoids on learning and on performance of diverse memory tasks in rodents (Fehr et al., 1976, Stiglick and Kalant, 1983, Nakamura et al., 1991, Brodkin and Moerschbaecher, 1997, Wise et al., 2009 and Robinson et al., 2010) and nonhuman primates (Zimmerberg et al., 1971, Galbicka et al., 1980, Winsauer et al., Vorinostat mouse 1999 and Nakamura-Palacios et al., 2000) are well documented (Lichtman et al, 2002), but efforts are needed to better understand the mechanisms underlying that impairment. It has long been appreciated that dopamine (DA) has a powerful influence on
the cognitive functions of the PFC, including WM (Brozoski et al., 1979, Sawaguchi NVP-BGJ398 datasheet and Goldman-Rakic, 1991, Goldman-Rakic, 1996, Zahrt et al., 1997, Lidow et al., 2003 and Robbins and Arnsten, 2009). Additionally, interactions between DA release and cannabinoids have been reported in several brain areas in vitro and in vivo (Gardner and Lowinson, 1991 and Fernández-Ruiz et al., 2010). These interactions consist in enhancement of DA release induced by cannabinoids (Poddar and Dewey, 1980, Jentsch et al., 1998 and Bossong et al., 2009), no effect of cannabinoids over dopaminergic neurons (Szabo et al., 1999), and inhibition of DA release (Cadogan et al., 1997). Probably these different data are due to the variability in brain area and applied methodology, but it shows how CYTH4 this theme needs to be more defined. To explore further the mechanisms by which Δ9-THC impairs WM, as previously reported by our laboratory, this study sought to determine if DA activation in the mPFC is directly involved in this disruption of WM induced by Δ9-THC. The dopamine antagonists SCH 23390 (SCH) and clozapine
(CZP) were used to investigate the involvement of D1-like and D2-like dopamine receptors, respectively, on Δ9-THC action in the mPFC. All data presented in this study were from animals whose cannulae were successfully implanted in the mPFC. Fig. 1 shows the proper location of the bilateral cannula. Most often, the cannulae were placed in the Cg1 and Cg3 areas from the anterior cingulate and prelimbic cortex, subareas of the mPFC, especially in the 3.7-, 3.2-, and 2.7-mm sections depicted in diagrams from Paxinos and Watson (1986). Moreover, all animals progressively improved in task performance in the radial maze. After 2 months of training, all animals achieved the baseline criterion of no more than one error in each of at least three consecutive sessions.