Serotonin, the prefrontal cortex, and the antidepressant-like effect of cannabinoids.

Editor's Note: These short reviews of a recent paper in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to mimic the journal clubs that exist in your own departments or institutions. For more information on the format and purpose of the Journal Club, please see Review of Bambico et al. The herb Cannabis sativa (marijuana) and its active component, ⌬ 9-tetrahydro-cannabinol (⌬ 9-THC), induce feelings of " high " and euphoria by activating canna-binoid type 1 receptors (CB 1 Rs) in the brain. The membrane-lipid derivates arachydonoil ethanolamide (nicknamed anandamide, after " ananda, " a Sanskrit word meaning " bliss ") and 2-arachydonoil glycerol, referred to as en-docannabinoids, are endogenous agonists at this receptor. Their action is terminated by uptake followed by catabolism by fatty acid amide hydrolase (FAAH) and mono-acylglycerol lipase, respectively (Marsi-cano and Lutz, 2006). Considering the influence of marijuana on emotional states, it has been hypothesized that enhancing CB 1 R activation , either with agonists or by blockade of FAAH, could be a strategy to develop new anxiolytic and antidepressant drugs (Gobbi et al., 2005; Moreira et al., 2008). The majority of clinically used antidepres-sants inhibit the reuptake of serotonin that seems to play a major role in the phys-iopathology of mood disorders. Recently, some results have suggested that seroto-nin may mediate the antidepressant-like effect of cannabinoids. For instance, FAAH inhibition promotes an increase in firing activity of serotonergic neurons in the dorsal raphe nucleus (Gobbi et al., 2005) and CB 1 R mRNA is expressed in these cells as well as in the surroundings (Haring et al., 2007). A recent paper, published in the Journal of Neuroscience by Bambico et al. (2007) provides more direct evidence to support this possibility. The authors tested the synthetic CB 1 R agonist