We found, as did others, that cannabinoid receptor densities did not change in cingulate and prefrontal cortices after social isolation (Malone et al., 2008). In contrast, schizophrenic patients exhibit increased cannabinoid receptor densities in these cortices compared to controls (Dean et al., 2001, Zavitsanou et al., 2004, Newell et al., 2006). Chronic-intermittent phencyclidine treated rats exhibit schizophrenia-like cognitive deficits and reductions in cannabinoid agonist-stimulated [35S]GTPγS binding in the prefrontal cortex compared to controls (Vigano et al., 2009). It is possible that similar changes also resulted from social isolation, but normalized before receptor densities were measured in adulthood. Experiments that elucidate the time course of changes in CB1 receptor densities and endocannabinoid content during the developmental window corresponding to adolescence (i.e., the social isolation manipulation window) are, therefore, warranted. It is particularly noteworthy that social isolation throughout adolescence in rats (present report), chronic-intermittent phencyclidine treatment in adolescent rats (Vigano et al., 2009), and exposure to repeated restraint stress in adolescent mice (Patel et al., 2005) all increased 2-AG, but not anandamide, in the prefrontal cortex (see also Seillier et al., 2009).
