Abstract
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 serotonin2A (5-HT2A) 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-HT2A 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-HT2A 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-HT2 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-HT2A 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-HT2A receptors may be altered by type-1 diabetes in mice.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alper RH (1990) Evidence for central and peripheral serotonergic control of corticosterone secretion in the conscious rat. Neuroendocrinology 51:255–260
Anderson RJ, Freedland KE, Clouse RE, Lustman PJ (2001) The prevalence of comorbid depression in adults with diabetes. A meta-analysis. Diabetes Care 24:1069–1078
Attar-Levy D, Martinot JL, Blin J, Dao-Castellana MH, Crouzel C, Mazoyer B, Poirier MF, Bourdel MC, Aymard N, Syrota A, Feline A (1999) The cortical serotonin2 receptors studied with positron-emission tomography and [18F]-setoperone during depressive illness and antidepressant treatment with clomipramine. Biol Psychiatry 45:180–186
Cameron OG, Kronfol Z, Greden JF, Carroll BJ (1984) Hypothalamic-pituitary-adrenocortical activity in patients with diabetes mellitus. Arch Gen Psychiatry 41:1090–1095
Chan O, Chan S, Inouye K, Vranic M, Matthews SG (2001) Molecular regulation of the hypothalamo-pituitary-adrenal axis in streptozotocin-induced diabetes: effects of insulin treatment. Endocrinology 142:4872–4879
Chan O, Inouye K, Vranic M, Matthews SG (2002) Hyperactivation of the hypothalamo-pituitary-adrenocortical axis in streptozotocin-diabetes is associated with reduced stress responsiveness and decreased pituitary and adrenal sensitivity. Endocrinology 143:1761–1768
Darmani NA, Martin BR, Pandey U, Glennon RA (1990) Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacol Biochem Behav 36:901–906
Gingrich JA, Zhou M, Sealfon S, Hen R (1999) Mice lacking the 5-HT2A receptor are insensitive to many of the behavioral and physiological effects of hallucinogens. Abstr Soc Neurosci 25:799
de Groot M, Anderson RJ, Freedland KE, Clouse RE, Lustman PJ (2001) Association of depression and diabetes complications: a meta-analysis. Psychosom Med 63:619–630
Handley SL, Brown J (1982) Effects on the 5-hydroxytryptamine-induced head-twitch of drugs with selective actions on alpha1 and alpha2-adrenoceptors. Neuropharmacology 21:507–510
Handley SL, Singh L (1985) Modulation of 5-hydroxytryptamine-induced head-twitch response by drugs acting at GABA and related receptors. Br J Pharmacol 86:297–303
Hosseinzadeh H, Nassiri Asl M (2003) Anticonvulsant, sedative and muscle relaxant effects of carbenoxolone in mice. BMC Pharmacol 3:3
Hoyer D, Pazos A, Probst A, Palacios JM (1986) Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res 376:97–107
Izumi T, Suzuki K, Inoue T, Li XB, Maki Y, Muraki I, Kitaichi Y, Hashimoto S, Koyama T (2002) Long-lasting change in 5-HT2A receptor-mediated behavior in rats after a single footshock. Eur J Pharmacol 452:199–204
Kamei J, Ohsawa M (1997) Role of noradrenergic functions in the modification of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes. Life Sci 60:PL223–PL228
Kamei J, Ohsawa M (2000) Socio-psychological stress-induced antinociception in diabetic mice. Psychopharmacology 149:397–400
Kamei J, Ohhashi Y, Aoki T, Kasuya Y (1991) Streptozotocin-induced diabetes in mice reduces the nociceptive threshold, as recognized after application of noxious mechanical stimuli but not of thermal stimuli. Pharmacol Biochem Behav 39:541–544
Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE (2000) Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care 23:934–942
McCall AL (1992) The impact of diabetes on the CNS. Diabetes 41:557–570
Meltzer HY, Umberkoman-Wiita B, Robertson A, Tricou BJ, Lowy M, Perline R (1984) Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. 1. Enhanced response in depression and mania. Arch Gen Psychiatry 41:366–374
Messa C, Colombo C, Moresco RM, Gobbo C, Galli L, Lucignani G, Gilardi MC, Rizzo G, Smeraldi E, Zanardi R, Artigas F, Fazio F (2003) 5-HT2A receptor binding is reduced in drug-naive and unchanged in SSRI-responder depressed patients compared to healthy controls: a PET study. Psychopharmacology 167:72–78
Mikuni M, Kusumi I, Kagaya A, Kuroda Y, Mori H, Takahashi K (1991) Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 15:49–61
Miyata S, Hirano S, Kamei J (2004) Diabetes attenuates the antidepressant-like effect mediated by the activation of 5-HT1A receptor in the mouse tail suspension test. Neuropsychopharmacology 29:461–469
Roy M, Collier B, Roy A (1990) Hypothalamic-pituitary-adrenal axis dysregulation among diabetic outpatients. Psychiatry Res 31:31–37
Sakuma T, Honma R, Maguchi S, Tamaki H, Nemoto N (2001) Different expression of hepatic and renal cytochrome P450s between the streptozotocin-induced diabetic mouse and rat. Xenobiotica 31:223–237
Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ (1995) (1-(2,5-Dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT)2A receptors: modulation by novel 5-HT2A/2C antagonist, D1 antagonists and 5-HT1A agonists. J Pharmacol Exp Ther 273:101–112
Shapiro ET, Polonsky KS, Copinschi G, Bosson D, Tillil H, Blackman J, Lewis G, Van Cauter E (1991) Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes. J Clin Endocrinol Metab 72:444–454
Takao K, Nagatani T, Kitamura Y, Yamawaki S (1997) Effects of corticosterone on 5-HT1A and 5-HT2 receptor binding and on the receptor-mediated behavioral responses of rats. Eur J Pharmacol 333:123–128
Welch JE, Saphier D (1994) Central and peripheral mechanisms in the stimulation of adrenocortical secretion by the 5-hydroxytryptamine2 agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. J Pharmacol Exp Ther 270:918–928
Willins DL, Meltzer HY (1997) Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats. J Pharmacol Exp Ther 282:699–706
Yatham LN, Liddle PF, Shiah IS, Scarrow G, Lam RW, Adam MJ, Zis AP, Ruth TJ (2000) Brain serotonin2 receptors in major depression: a positron emission tomography study. Arch Gen Psychiatry 57:850–858
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Miyata, S., Hirano, S. & Kamei, J. Diabetes inhibits the DOI-induced head-twitch response in mice. Psychopharmacology 177, 224–229 (2004). https://doi.org/10.1007/s00213-004-1942-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-004-1942-3