In isolates, deprivation of olfactory cues from littermates produces conditioned odor deficits (Zimmerberg et al., 2009). Moreover, social isolation alters several neurotransmitter systems in brain regions involved in olfaction; social isolation increases 2-AG and anandamide levels in the piriform cortex (present report) and increases cholinergic and serotonergic fiber densities in the olfactory bulb and piriform cortex (Lehmann and Lehmann, 2007). Deficits in olfactory-related behaviors and circuitry may worsen the impaired interaction isolates have with their environment (for review see Fone and Porkess, 2008). Along the same line, we show social isolation alters the endocannabinoid system in the supraoptic nucleus of the hypothalamus. The supraoptic nucleus, a brain region implicated in social behaviors, is part of the magnocellular neurosecretory system of the hypothalamus (Martin, 2003). Input to oxytocin synthesizing neurons of the supraoptic nucleus is modulated by endocannabinoids that act at CB1 receptors (McDonald et al., 2008). It is interesting to speculate that downregulation of cannabinoid receptors observed here in socially-isolated rats is associated with increased endocannabinoid signaling; such changes would be expected to modify GABA-ergic and glutamatergic inputs to oxytocin
