Dopamine neurotransmission is involved in the attenuating effects of 5-HT3 receptor antagonist MDL 72222 on acute methamphetamine-induced locomotor hyperactivity in 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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The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist

Journal of Neural Transmission ◽

10.1007/bf01292622 ◽

1996 ◽

Vol 103 (1-2) ◽

pp. 131-146 ◽

Cited By ~ 17

Author(s):

J. Maj ◽

Z. Rogóż ◽

G. Skuza ◽

K. Wędzony

Keyword(s):

Nmda Receptor ◽

Synergistic Effect ◽

Receptor Antagonist ◽

Nmda Receptor Antagonist ◽

Locomotor Hyperactivity ◽

Mk 801

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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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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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