Central neurotransmitter receptor binding and behaviour during streptozotocin-induced diabetes mellitus in rats

The high affinity binding sites were investigated in frontal cortical serot onin, striatal dopamine, hippocampal muscarinic cholinergic and benzodiazep ine receptors in the brains of 3-day diabetic and insulin treated Charles F oster rats. Locomotor activity and conditioned avoidance response (CAR) wer e also studied. Diabetes was induced by injecting streptozotocin (STZ) (50m g/kg i.p.). Insulin was given from the day of STZ injection. One group of r ats was kept under insulin therapy throughout the behavioral studies. The r esults indicate that diabetic rats exhibit increased striatal (3)[H] spirop eridol, hippocampal (3)[H] flurazepam and (3)[H] quinuclidinyl benzilate (Q NB) binding sites and decreased frontal cortical 3[H] serotonin binding sit es. The increased receptor binding sites were found to be due to increase i n the number of receptor (B-max) levels and not due to affinity (K-D) chang e. Diabetic rats exhibited decreased locomotor activity. CAR Learning acqui sition was inhibited but no retention deficits were noted in diabetic rats. However, conditioned and anticipatory conditioned avoidance responses were significantly high and low, respectively, both in learning and retention s tudies. Insulin treatment reversed the brain receptor alteration and behavi oral changes, The data suggest, that in early diabetic condition there is a n upregulation of striatal dopamine, hippocampal muscarinic cholinergic and benzodiazepine receptors, whereas frontal cortical serotonin receptors are down regulated, which may explain the CAR acquisition deficits, decreased locomotor activity and the anxiogenic behavior pattern reported earlier.