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


OBJECTIVE
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.
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, 142-8501, Japan.
Shigeo
S
Miyata
Shoko
S
Hirano
Junzo
J
Kamei
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D019416:Head Movements / Q000187:drug effects* / Q000502:physiology*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone