Rats with anxious or non-anxious type of exploratory behaviour differ in their brain CCK-8 and benzodiazepine receptor characteristics

Abstract

Rats with high and low exploratory activity in an elevated plus-maze model of anxiety were separated into subgroups termed ‘non-anxious’ and ‘anxious’ respectively according to the number of sectors the animals crossed and the total amount of time they spent in the open part of the plus-maze. The binding parameters of benzodiazepine and cholecystokinin octapeptide (CCK-8) receptors in frontal cortex and hippocampus of selected animals were studied and compared to an animal group representing the total mean scores and to home-cage controls. It was established that anxious rats had a significantly lower number of benzodiazepine receptors in frontal cortex as compared to non-anxious animals and in hippocampus as compared to home-cage controls. There was also a decreased number of CCK-8 receptors in hippocampus of anxious rats as compared to the non-anxious and control groups. Non-anxious animals had a significantly lower number of CCK-8 receptors in frontal cortex than anxious and control rats. Acute treatment of rats with anxiogenic benzodiazepine inverse agonist FG 7142 (10 and 20 mg/kg) did not influence benzodiazepine binding in brain regions under investigation but caused upregulation of CCK-8 receptor binding in frontal cortex. On the other hand, CCK-8 analogues caerulein and pentagastrin, administered in doses which inhibit exploratory activity in plus-maze (100 or 500 ng/kg respectively), decreased the number of benzodiazepine binding sites in rat frontal cortex if injected intraperitoneally but did not affect CCK-8 binding. The present findings indicate that benzodiazepine and CCK-8 receptor binding characteristics in brain undergo rapid and behaviourally specific changes during stressful events.