Social isolation of rats increases the density of cholecystokinin receptors in the frontal cortex and abolishes the anti-exploratory effect of caerulein.

The role of cholecystokinin (CCK) receptors in the development of anxiety caused by social isolation of rats was studied using the elevated plus-maze and receptor binding techniques. The isolation of male Wistar rats significantly reduced their exploratory activity in the elevated plus-maze compared with that of rats kept in groups of four. Caerulein (0.1-5 micrograms/kg s.c.), an agonist at CCK receptors, only at the highest dose (5 micrograms/kg) significantly decreased the exploratory behaviour of rats housed in groups, but not in the isolated rats. By contrast, small doses of caerulein (0.1-0.5 microgram/kg) even tended to increase the behavioural activity of isolated rats in the plus-maze test. In parallel to the behavioural changes, isolation of the rats increased the number of [3H]pCCK-8 binding sites in the frontal cortex, but not in the other forebrain structures (the mesolimbic area, striatum and hippocampus). Isolation did not affect the density of benzodiazepine receptors in the frontal cortex. In conclusion, the isolation of rats for 7 days produced anxiogenic-like effect on the behaviour of rats and increased the number of CCK receptors in the frontal cortex without affecting benzodiazepine receptors.