Abstract
The aim of the present study was to investigate the role of central 5-HT3 receptors on the control of blood glucose in stressed and non-stressed rats in both fasted and fed states. Adult Wistar male rats had each their third ventricle cannulated 7 days before the experiments. Injections of m-CPBG, a selective 5-HT3 receptor agonist, induced a significant increase in blood glucose in non-stressed rats in both fasted and in fed states. The same procedure was unable to modify stress-induced hyperglycemia. The hyperglycemic effect of m-CPBG central administration was blocked by pretreatment with ondansetron, a specific 5-HT3 receptor antagonist, indicating that the effects here obtained with m-CPBG were a result of its interaction with 5-HT3 receptors. Third ventricle injections of ondansetron alone were not able to modify blood glucose in non-stressed animals and did not change the hyperglycemic responses observed after immobilization stress. We conclude that pharmacological activation of the central 5-HT3 receptor induces a hyperglycemic effect in non-stressed animals.
Key words
Serotonin - Stress - Blood Glucose - Hyperglycemia - 5-HT3 Receptor
References
1
Chaouloff F, Jeanrenaud B.
5-HT1A and alpha-2 adrenergic receptors mediate the hyperglycemic and hypoinsulinemic effects of 8-hydroxy-2-(di-n-propylamino) tetralin in conscious rat.
J Pharmacol Exp Ther.
1987;
243
1159-1166
2
Chaouloff F, Laude D, Baudrie V.
Effects of the 5-HT1C /5-HT2 receptor agonists DOI and α-methyl-5-HT on plasma glucose and insulin levels in the rat.
Eur J Pharmacol.
1990;
187
435-443
3
Chaouloff F, Gunn S H, Young J B.
Central 5-hydroxytryptamine2 receptors are involved in the adrenal catecholamine-releasing and hyperglycemic effects of the 5-hydroxytryptamine indirect agonist d-fenfluramine in the conscious rat.
J Pharmacol Exp Ther.
1992;
260
1008-1016
4
Durcan M J, Wozniak K M, Linnoila M.
Modulation of the hypothermia and hyperglycaemic effects of 8-OH-DPAT by α2-adrenoceptor antagonists.
Br J Pharmacol.
1991;
102
222-226
5
Sugimoto Y, Yamada J, Yoshikawa T, Horisaka K.
Effects of the 5-HT2B/2C receptor agonist l-(3-chlorophenyl)piperazine on the plasma glucose levels of rats.
Eur J Pharmacol.
1996;
307
75-80
6
Yamada J, Sugimoto Y, Yoshikawa T.
p-Chloroamphetamine, a serotonin-releasing drug, elicited in rats a hyperglycemia mediated by the 5-HT1A and 5-HT2B/2C receptors.
Eur J Pharmacol.
1998;
359
185-190
7
Luiten P GM, Ter Horst G J, Steffens A B.
The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism.
Prog Neurobiol.
1987;
28
1-54
8
Wozniak K M, Linnoila M.
Hyperglycemic properties of serotonin receptor antagonists.
Life Sci.
1991;
49
101-109
9
Korte S M, van Duin S, Bouws G A, Koolhaas J M, Bohus B.
Involvement of hypothalamic serotonin in activation of the sympathoadrenomedullary system and hypothalamo-pituitary-adrenocortical axis in male Wistar rats.
Eur J Pharmacol.
1991;
197
225-228
10
Chaouloff F, Laude D, Baudrie V.
Ganglionic transmission is a prerequisite for the adrenaline-releasing and hyperglycemic effects of 8-OH-DPAT.
Eur J Pharmacol.
1990;
185
11-18
11
Chrousos G P, Gold P W.
The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis.
J Am Med Assoc.
1992;
267
1244-1252
12
Chaouloff F.
Physiopharmacological interactions between stress hormones and central serotonergic systems.
Brain Res Rev.
1993;
18
1-32
13
Harms P G, Ojeda S R.
A rapid and simple procedure for chronic cannulation of rat jugular vein.
J Appl Physiol.
1974;
36
391-394
14
Kilpatrick G J, Butler A, Burridge J, Oxford A W.
l-(m-Chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist.
Eur J Pharmacol.
1990;
182
193-197
15
Gaster L M, King F D.
Serotonin 5-HT3 and 5-HT4 receptor antagonists.
Med Res Rev.
1997;
17
163-214
16
Yamada J, Sugimoto Y, Inoue K.
Selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms.
Eur J Pharmacol.
1999;
382
211-215
17
Nonogaki K, Iguchi A.
Role of central neural mechanisms in the regulation of hepatic glucose metabolism.
Life Sci.
1997;
60
797-807
18
Shimazu T, Fukuda A, Ban T.
Reciprocal influences of the ventromedial and lateral hypothalamic nuclei on blood glucose level and liver glycogen content.
Nature.
1966;
210
1178-1179
19
Iguchi A, Kunoh Y, Miura H, Uemura K, Yatomi A, Tamagawa T, Kawahara H, Sakamoto N.
Central nervous system control of glycogenolysis and gluneogenesis in fed and fasted rat liver.
Metabolism.
1989;
38
1216-1221
20
Baudrie T, Chaouloff F.
Mechanisms involved in the hyperglycemic effect of the 5-HT1C /5-HT2 receptor agonist DOI.
Eur J Pharmacol.
1992;
213
41-46
21
Bloom F E, Morales M.
The central 5-HT3 receptor in CNS disorders.
Neurochem Res.
1998;
23
653-659
22
Peters J, Lambert J.
Electrophysiology of 5-HT3 receptors in neuronal cell lines.
Trends Pharmacol Sci.
1989;
10
172-174
23
Nonogaki K, Iguchi A.
Role of central neural mechanisms in the regulation of hepatic glucose metabolism.
Life Sci.
1997;
60
797-807
24
Diez-Ariza M, Ramirez M J, Lasheras B, Del Rio J.
Differential interaction between 5-HT3 receptors and GABAergic neurons inhibiting acetylcholine release in rat enthorhinal cortex slices.
Brain Res.
1998;
801
228-232
25
Bames J M, Barnes N M, Costall B, Naylor R J, Tyers M B.
5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue.
Nature.
1989;
338
762-763
26
Jansen A S, Nguyen X V, Karpitskiy V, Mettenleiter T C, Loewy A D.
Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response.
Science.
1995;
270
644-646
27
Chaouloff F, Berton O, Mormede P.
Serotonin and stress.
Neuropsychopharmacol.
1999;
21
28S-32S
28
Badgy G, Calogero A E, Murphy D, Szemeredi K.
Serotonin agonists cause parallel activation of sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats.
Endocrinol.
1989;
165
2664-2669
29
Doherty K M.
Closing the gap in prophylactic antiemetic therapy: patient factors in calculating the emetogenic potential of chemotherapy.
Clin J Oncol Nurs.
1999;
3
113-119
Emilio de Castro e Silva, M.D., Ph.D.
Universidade Federal da Bahia · Institute de Ciências da Saúde · Departamento de Fisiologia
40110-100 Salvador - BA · Brasil