Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice

Previous studies from our laboratory indicate that acute but not chronic hypoxia decreases the hemorrhage volume required to elicit reflex hypotension. Furthermore, chronically hypoxic animals exhibit an elevated hypotensive threshold during both normoxia and hypoxia compared with control animals. Because reports suggest that opioid and serotonergic mechanisms may be involved in mediating the sympathoinhibition that occurs with hemorrhage, we hypothesized that opioid and/or serotonergic systems are stimulated during hemorrhage under conditions of acute hypoxia and suppressed after chronic exposure to hypoxia and are thus responsible for the altered cardiovascular responses to hemorrhage under each condition. Control and chronically hypoxi rats were administered either the opioid receptor antagonist naltrexone (1 mg/kg), the selective 5-hydroxytryptamine receptor subtype 3 (5-HT3) serotonergic receptor antagonist MDL-72222 (0.5 mg/kg), or their respective vehicles intravenously before hemorrhage was initiated during normoxia or hypoxia (FIO2 = 0.12). In control animals, pretreatment with naltrexone increased the hemorrhage was initiated volume required to achieve hypotension in hypoxic but not normoxic conditions. Naltrexone had no effect on hypotensive threshold in chronically hypoxic animals under conditions of either normoxia or hypoxia. In addition, MDL-72222 had no effect on hypotensive threshold in either control or chronically hypoxic animals in either normoxic or hypoxic conditions. We conclude that endogenous opioids may contribute to the reflex hypotension that occurs during hypoxic hemorrhage in control rats, while no such involvement is evident in chronically hypoxic animals. Furthermore, peripheral 5-HT3 receptors are not likely involved in this response during either normoxic or hypoxic hemorrhage in control or chronically hypoxic rats.

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Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-004-0939-0 ◽

2004 ◽

Vol 369 (6) ◽

pp. 547-553 ◽

Cited By ~ 78

Author(s):

E. C. Gavioli ◽

C. W. Vaughan ◽

G. Marzola ◽

R. Guerrini ◽

V. A. Mitchell ◽

...

Keyword(s):

Receptor Antagonist ◽

Orphanin Fq ◽

Rats And Mice ◽

New Evidence

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5-HT 3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not methylphenidate-induced neurochemical and behavioral effects in the rat

Psychopharmacology ◽

10.1007/s00213-001-0939-4 ◽

2002 ◽

Vol 159 (4) ◽

pp. 341-350 ◽

Cited By ~ 43

Author(s):

Aino Kankaanpää ◽

Esa Meririnne ◽

Timo Seppälä

Keyword(s):

Receptor Antagonist ◽

Behavioral Effects ◽

Mdl 72222

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YQA14: a novel dopamine D3 receptor antagonist that inhibits cocaine self-administration in rats and mice, but not in D3 receptor-knockout mice

Addiction Biology ◽

10.1111/j.1369-1600.2011.00317.x ◽

2011 ◽

Vol 17 (2) ◽

pp. 259-273 ◽

Cited By ~ 66

Author(s):

Rui Song ◽

Ri-Fang Yang ◽

Ning Wu ◽

Rui-Bin Su ◽

Jin Li ◽

...

Keyword(s):

Receptor Antagonist ◽

Knockout Mice ◽

Dopamine D3 Receptor ◽

D3 Receptor ◽

Self Administration ◽

Dopamine D3 ◽

Rats And Mice

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Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures

Acta Endocrinologica ◽

10.1530/eje.0.1330251 ◽

1995 ◽

Vol 133 (2) ◽

pp. 251-254 ◽

Cited By ~ 25

Author(s):

Aldo E Calogero ◽

Gyorgy Bagdy ◽

Nunziatina Burrello ◽

Pietro Polosa ◽

Rosario D'Agata

Keyword(s):

Pituitary Gland ◽

Receptor Antagonist ◽

Cell Cultures ◽

Adrenocorticotropic Hormone ◽

Pituitary Cell ◽

Hormone Release ◽

Mdl 72222 ◽

Rat Pituitary ◽

Ics 205 930 ◽

Acth Release

Calogero AE, Bagdy G, Burrello N, Polosa P. D'Agata R. Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures. Eur J Endocrinol 1995;133:251–4. ISSN 0804–4643 Although several serotonin (5-HT) receptor types have been shown capable of stimulating the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, relatively little is known about the role of the 5-HT3 receptor, a receptor that has generated a great deal of interest for its involvement in many behavioral and therapeutic effects. Hence, in this study, we tested the effects of the 5-HT¾ receptor antagonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) and the selective 5-HT3 receptor antagonist 3-tropanyl-3,5-dichlorobenzoate (MDL 72222) on ACTH release stimulated by 5-HT from primary cultures of rat pituitary cells. Subsequently, we evaluated the effects of the selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG) on basal, corticotropin-releasing hormone (CRH)- and arginine vasopressin (AVP)-stimulated ACTH release. The maximal stimulatory effect of 5-HT (10−9 mol/l on ACTH release was antagonized by both ICS 205-930 and MDL 72222, suggesting that 5-HT stimulates basal ACTH release through activation of 5-HT3 receptors. Accordingly, m-CPBG stimulated basal ACTH release in a concentration-dependent fashion. In contrast to 5-HT, m-CPBG did not have any effect on CRH-stimulated ACTH release and inhibited AVP-stimulated ACTH release in a concentration-dependent manner. These data suggest that the 5-HT3 receptor is involved in the release of ACTH from the pituitary gland in vitro. Aldo E Calogero, Istituto di Clinica Medica I, Ospedale Garibaldi, Piazza S Maria di Gesú, 95123 Catania, Italy

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The interleukin-1 receptor antagonist influences interleukin-1 effects in rat and mouse

Mediators of Inflammation ◽

10.1155/s0962935192000061 ◽

1992 ◽

Vol 1 (1) ◽

pp. 27-31 ◽

Cited By ~ 1

Author(s):

P. Bjrök ◽

K. Ohlsson

Keyword(s):

Receptor Antagonist ◽

Acute Phase ◽

Acute Phase Protein ◽

Interleukin 1 ◽

Interleukin 1 Receptor Antagonist ◽

Acute Phase Protein Response ◽

Phase Protein ◽

Protein Response ◽

Rats And Mice

In this work we have focused on the ability of interleukin-1 to induce an acute phase protein response and a degranulation of polymorphonuclear leukocytes in vivo. The capacity of the interleukin-1 receptor antagonist to influence these events was also investigated. It was shown that interleukin-1 induced an acute phase protein response in rats and mice. In rats α2-macroglubolin levels were increased in plasma after an interleukin-1 injection whereas α1-inhibitor-3 decreased in plasma. In the mice plasma amyloidPwas increased. The interleukin-1 receptor antagonist blocked the increase of α2-macroglobulin and plasma amyloidPin a dose dependent way while the effect on the α1-inhibitor-3 decrease was less pronounced. Interleukin-1 led to polymorphonuclear leukocyte degranulation in vivo as measured by increased cathepsinGplasma levels. The interleukin-1 receptor antagonist could influence the early phase of this degranulation.

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