Research reportBlood glucose regulation mechanism in depressive disorder animal model during hyperglycemic states

- Chronic stress-induced depression animal model.
- Increased blood glucose level induced by various hyperglycemia conditions.
- Increased blood glucose level is reduced in depression group.
- Attenuation of corticosterone level in the depression group might be responsible.
- Possible involvement of centrally located α2-adrenergic receptors.

Depression is more common among diabetes people than in the general population. In the present study, blood glucose change in depression animal model was characterized by various types of hyperglycemia models such as d-glucose-fed-, immobilization stress-, and drug-induced hyperglycemia models. First, the ICR mice were enforced into chronic restraint stress for 2 h daily for 2 weeks to produce depression animal model. The animals were fed with d-glucose (2 g/kg), forced into restraint stress for 30 min, or administered with clonidine (5 μg/5 μl) supraspinally or spinally to produce hyperglycemia. The blood glucose level in depression group was down-regulated compared to that observed in the normal group in d-glucose-fed-, restraint stress-, and clonidine-induced hyperglycemia models. The up-regulated corticosterone level induced by d-glucose feeding or restraint stress was reduced in the depression group while the up-regulation of plasma corticosterone level is further elevated after i.t. or i.c.v. clonidine administration in the depression group. The up-regulated insulin level induced by d-glucose feeding or restraint stress was reduced in the depression group. On the other hand, blood corticosterone level in depression group was up-regulated compared to the normal group after i.t. or i.c.v. clonidine administration. Whereas the insulin level in depression group was not altered when mice were administered clonidine i.t. or i.c.v. Our results suggest that the blood glucose level in depression group is down-regulated compared to the normal group during d-glucose-fed-, immobilization stress-, and clonidine-induced hyperglycemia in mice. The down-regulation of the blood glucose level might be one of the important pathophysiologic changes in depression.