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

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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N-methyl-D-aspartate receptor antagonist activity and phencyclidine-like behavioral effects of the pentadecapeptide, [Ser1]histogranin

Pharmacology Biochemistry and Behavior ◽

10.1016/0091-3057(94)00247-g ◽

1995 ◽

Vol 50 (1) ◽

pp. 49-54 ◽

Cited By ~ 19

Author(s):

Vijay K. Shukla ◽

Simon Lemaire ◽

Michel Dumont ◽

Zul Merali

Keyword(s):

Receptor Antagonist ◽

Behavioral Effects ◽

Antagonist Activity ◽

Aspartate Receptor

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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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Behavioral Effects of γ-Hydroxybutyrate, Its Precursor γ-Butyrolactone, and GABAB Receptor Agonists: Time Course and Differential Antagonism by the GABAB Receptor Antagonist 3-Aminopropyl(diethoxymethyl)phosphinic Acid (CGP35348)

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.109.151845 ◽

2009 ◽

Vol 330 (3) ◽

pp. 876-883 ◽

Cited By ~ 18

Author(s):

Wouter Koek ◽

Susan L. Mercer ◽

Andrew Coop ◽

Charles P. France

Keyword(s):

Receptor Antagonist ◽

Time Course ◽

Gabab Receptor ◽

Phosphinic Acid ◽

Behavioral Effects ◽

Receptor Agonists ◽

Gabab Receptor Antagonist

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Blockade of Serotonin 2C Receptors with SB-242084 Moderates Reduced Locomotor Activity and Rearing by Cannabinoid 1 Receptor Antagonist AM-251

Pharmacology ◽

10.1159/000495939 ◽

2019 ◽

Vol 103 (3-4) ◽

pp. 151-158 ◽

Cited By ~ 1

Author(s):

Emese Bogáthy ◽

Diana Kostyalik ◽

Peter Petschner ◽

Szilvia Vas ◽

Gyorgy Bagdy

Keyword(s):

Locomotor Activity ◽

Receptor Antagonist ◽

Cb1 Receptor ◽

Behavioral Effects ◽

Receptor Antagonists ◽

Plus Maze ◽

Male Wistar Rats ◽

Cb1 Receptor Antagonist ◽

Cb1 Receptor Antagonists ◽

Sb 242084

The endocannabinoid and serotonin (5-HT) systems have key roles in the regulation of several physiological functions such as motor activity and food intake but also in the development of psychiatric disorders. Here we tested the hypothesis, whether blockade of serotonin 2C (5-HT2C) receptors prevents the reduced locomotor activity and other behavioral effects caused by a cannabinoid 1 (CB1) receptor antagonist. As a pretreatment, we administered SB-242084 (1 mg/kg, ip.), a 5-HT2C receptor antagonist or vehicle (VEH) followed by the treatment with AM-251 (5 or 10 mg/kg, ip.), a CB1 receptor antagonist or VEH. The effects of the two drugs alone or in co-administration were investigated in social interaction (SI) and elevated plus maze (EPM) tests in male Wistar rats. Our results show that AM-251 decreased the time spent with rearing in the SI test and decreased locomotor activity in EPM test. In contrast, SB-242084 produced increased locomotor activity in SI test and evoked anxiolytic-like effect in both SI and EPM tests. When applied the drugs in combination, these behavioral effects of AM-251 were moderated by SB-242084. Based on these findings, we conclude that certain unwanted behavioral effects of CB1 receptor antagonists could be prevented by pretreatment with 5-HT2C receptor antagonists.

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