Chronic stress differentially regulates cannabinoid CB1 receptor binding in distinct hippocampal subfields

Abstract

Exposure to chronic stress has been found to decrease cannabinoid CB(1) receptor expression in the hippocampus; however, the specificity of this phenomenon to specific subfields of the hippocampus has not been characterized. To this extent, male Sprague-Dawley rats were exposed to 21 days of restraint stress (6 h/day), after which autoradiographical analysis of cannabinoid CB(1) receptor binding site densities were examined in the CA1, CA3 and dentate gyrus subfields of the hippocampus. Chronic stress was found to produce a significant reduction in cannabinoid CB(1) receptor binding in the dentate gyrus, while increasing cannabinoid CB(1) receptor binding in the CA3. There was no effect of chronic stress on cannabinoid CB(1) receptor binding in the CA1, or two other proximal regions, the retrosplenial cortical gyrus and the laterodorsal thalamus. Given the role of hippocampal cannabinoid CB(1) receptor activity in the maintenance of synaptic integrity and neuroplasticity in the hippocampus, these data suggest that changes in cannabinoid CB(1) receptor activity following stress may contribute to stress-induced modulation of these processes.

Figure 1

The effect of chronic restraint stress (CRS; 21 days at 6 h/day) on cannabinoid CB₁ receptor binding in the (a) dentate gyrus, (b) CA3 and (c) CA1 subfields of the hippocampus. Values are denoted as mean relative optical density (R.O.D.) ± S.E.M. * denotes significant differences relative to all other treatment conditions (n= 7–8/condition). (d) Representative autoradiograms of the effects of chronic restraint stress (CRS) on cannabinoid CB₁ receptor binding throughout the hippocampus.