Social and environmental enrichment enhances sensitivity to the effects of kappa opioids: studies on antinociception, diuresis and conditioned place preference

Previous studies have reported that social and environmental enrichment can have a marked impact on the functional maturation of the central nervous system and may influence an organism's sensitivity to psychotropic drugs. The purpose of the present study was to examine the effects of social and environmental enrichment on sensitivity to drugs possessing activity at the kappa opioid receptor. Rats were obtained at weaning and randomly assigned to one of two housing conditions: isolated rats were housed individually with no visual or tactile contact with other rats; enriched rats were housed in groups of four in large cages and given various novel objects on a regular basis. After 7 weeks under these conditions, the effects of spiradoline, U69,593 and nalorphine were examined in the warm water, tail-withdrawal procedure. The effects of spiradoline were also examined on urine output and in the conditioned place preference procedure. Enriched rats were more sensitive to the antinociceptive effects of all the opioids examined in the tail-withdrawal procedure, and were more sensitive to the effects of spiradoline on urine output and in the conditioned place preference procedure. Following the conclusion of these tests, housing conditions were reassigned, such that isolated rats were transferred to enrichment cages, and enriched rats were transferred to isolation cages. After 7 weeks under these new conditions, the two groups were equally sensitive to the antinociceptive effects of spiradoline, indicating that the effects of the initial housing conditions were, in part, reversible. Collectively, these data suggest that enriched rats are more sensitive than isolated rats to the effects of kappa opioids, and that the kappa opioid receptor system is sensitive to social and environmental manipulations after weaning.