Diabetes inhibits the DOI-induced head-twitch response in mice.

RATIONALE

Clinical studies suggest that the prevalence of psychiatric disorders is higher in diabetic patients than in the general population. It has been reported that central serotonin(2A) (5-HT(2A)) receptors may be involved in the pathogenesis and treatment of psychiatric disorders.

OBJECTIVES

We examined the effect of streptozotocin-induced diabetes on the function of central 5-HT(2A) receptors in mice.

METHODS

Male ICR mice were rendered diabetic by an injection of streptozotocin (200 mg/kg, i.v.). The experiments were conducted 2 weeks after the injection of streptozotocin. To evaluate the central 5-HT(2A) receptor function, head-twitch responses were measured for 15 min immediately after the treatment with (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) (0.1-1 mg/kg, s.c.), a selective 5-HT(2) receptor agonist.

RESULTS

Significantly fewer head-twitch responses were induced by DOI in diabetic mice than in non-diabetic mice. The number and affinity of 5-HT(2A) receptors in the mouse frontal cortex were not affected by diabetes. The corticosterone response to DOI (1 mg/kg and 3 mg/kg, s.c.) was not different between non-diabetic and diabetic mice, although the baseline of plasma corticosterone levels was significantly higher in diabetic than in non-diabetic mice.

CONCLUSIONS

Our results suggest that a neuronal network that causes head-twitch responses by triggering by the activation of 5-HT(2A) receptors may be altered by type-1 diabetes in mice.