In socially isolated rats, chronic experimenter handling was not sufficient to modify cannabinoid receptor densities in the caudate putamen and thalamus; handling increased cannabinoid receptor densities in these same structures in group-, but not isolation-reared rats. Handling has been shown to preferentially reverse corticosterone levels in mice bred for low aggressiveness, but failed to reverse corticosterone levels in mice bred for high aggressiveness (Gariépy et al., 2002). Thus, it is, perhaps, not surprising that chronic handling did not reverse the array of changes induced by social isolation on the endocannabinoid system. Overall, we interpret our data to suggest that handling alone produces regulatory changes in the endocannabinoid system, but the effectiveness of this manipulation on the endocannabinoid system is diminished in rats reared in social deprivation.