Handling increased cannabinoid receptor densities in the limbic loop of the basal ganglia, including basal ganglia output structures (lateral globus pallidus) and allocortical areas (cingulate and piriform cortex), but decreased cannabinoid receptor densities in archicortex (hippocampus), relative to non-handling. Handling, like subchronic treatment with the antipsychotic haloperidol (Andersson et al., 2005), increased [3H]CP55,940 binding to cannabinoid receptors in the globus pallidus. In the piriform cortex, handling altered both endocannabinoid content and cannabinoid receptor densities in a manner consistent with a causal relationship between these factors. Handling-induced reductions in anandamide levels may produce the observed upregulation of cannabinoid receptors in this region. In archicortex, chronic handling decreased cannabinoid receptor densities relative to non-handling. If chronic handling decreases the number of cannabinoid receptors available to inhibit calcium influx into glutamatergic neurons, it is reasonable to speculate handling might also enhance long-term potentiation. Supporting this hypothesis, both acute handling (Korz and Frey, 2003) and social isolation (Lu et al., 2003) reverse long-term potentiation generated by tetanic stimulation in the hippocampus. In contrast, male rats exposed to early maternal deprivation – a model of
