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Diabetes inhibits the DOI-induced head-twitch response in mice
Shigeo Miyata1, Shoko Hirano, Junzo Kamei
1Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, 142-8501, Japan.
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.