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3,4-N-methlenedioxymethamphetamine-induced hypophagia is maintained in 5-HT1B receptor knockout mice, but suppressed by the 5-HT2C receptor antagonist RS102221.
Neuropsychopharmacology. 2005 Jun; 30(6):1056-63.N

Abstract

3,4-Methylenedioxy-N-methamphetamine (MDMA or 'ecstasy') is a psychoactive substance, first described as an appetite suppressant in humans, inducing side effects and even death. MDMA increases serotonin (5-HT) levels, and 5-HT inhibits food intake, but the 5-HT receptors involved in MDMA-induced changes in feeding behavior are unknown. We examined whether a systemic MDMA injection would reduce the physiological drive to eat in starved mice and tested if the inactivation of 5-HT1B or 5-HT2C receptors could restore this response. Our results indicate that in starved mice, MDMA (10 mg/kg) provoked an initial hypophagia for 1 h (-77%) followed by a period of hyperphagia (studied between 1 and 3 h). This biphasic feeding behavior due to MDMA treatment was maintained in 5-HT1B receptor-null mice or in animals treated with the 5-HT1B/1D receptor antagonist GR127935 (3 or 10 mg/kg). In contrast, MDMA-induced hypophagia (for the first 1 h period) was suppressed when combined with the 5-HT2C receptor antagonist RS102221 (2 mg/kg). However, RS102221 did not alter MDMA-induced hyperphagia (for the 1-3 h period) but did exert a stimulant effect, when administered alone, during that period. We have previously shown that MDMA or 5-HT1A/1B receptor agonist RU24969 fails to stimulate locomotor activity in 5-HT1B receptor-null mice. Our present data indicate that the 5-HT2C receptor antagonist RS102221 suppresses MDMA-induced hyperlocomotion. These findings provide the first evidence that the inactivation of 5-HT2C receptors may reduce hypophagia and motor response to MDMA, while a genetic deficit or pharmacological inactivation of 5-HT1B receptors was insufficient to alter the feeding response to MDMA.

Authors+Show Affiliations

UPR CNRS 5203, Génomique Fonctionnelle, Montpellier Cedex, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15668722

Citation

Conductier, Grégory, et al. "3,4-N-methlenedioxymethamphetamine-induced Hypophagia Is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed By the 5-HT2C Receptor Antagonist RS102221." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 30, no. 6, 2005, pp. 1056-63.
Conductier G, Crosson C, Hen R, et al. 3,4-N-methlenedioxymethamphetamine-induced hypophagia is maintained in 5-HT1B receptor knockout mice, but suppressed by the 5-HT2C receptor antagonist RS102221. Neuropsychopharmacology. 2005;30(6):1056-63.
Conductier, G., Crosson, C., Hen, R., Bockaert, J., & Compan, V. (2005). 3,4-N-methlenedioxymethamphetamine-induced hypophagia is maintained in 5-HT1B receptor knockout mice, but suppressed by the 5-HT2C receptor antagonist RS102221. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 30(6), 1056-63.
Conductier G, et al. 3,4-N-methlenedioxymethamphetamine-induced Hypophagia Is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed By the 5-HT2C Receptor Antagonist RS102221. Neuropsychopharmacology. 2005;30(6):1056-63. PubMed PMID: 15668722.
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TY - JOUR T1 - 3,4-N-methlenedioxymethamphetamine-induced hypophagia is maintained in 5-HT1B receptor knockout mice, but suppressed by the 5-HT2C receptor antagonist RS102221. AU - Conductier,Grégory, AU - Crosson,Cyril, AU - Hen,René, AU - Bockaert,Joël, AU - Compan,Valérie, PY - 2005/1/26/pubmed PY - 2005/7/12/medline PY - 2005/1/26/entrez SP - 1056 EP - 63 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 30 IS - 6 N2 - 3,4-Methylenedioxy-N-methamphetamine (MDMA or 'ecstasy') is a psychoactive substance, first described as an appetite suppressant in humans, inducing side effects and even death. MDMA increases serotonin (5-HT) levels, and 5-HT inhibits food intake, but the 5-HT receptors involved in MDMA-induced changes in feeding behavior are unknown. We examined whether a systemic MDMA injection would reduce the physiological drive to eat in starved mice and tested if the inactivation of 5-HT1B or 5-HT2C receptors could restore this response. Our results indicate that in starved mice, MDMA (10 mg/kg) provoked an initial hypophagia for 1 h (-77%) followed by a period of hyperphagia (studied between 1 and 3 h). This biphasic feeding behavior due to MDMA treatment was maintained in 5-HT1B receptor-null mice or in animals treated with the 5-HT1B/1D receptor antagonist GR127935 (3 or 10 mg/kg). In contrast, MDMA-induced hypophagia (for the first 1 h period) was suppressed when combined with the 5-HT2C receptor antagonist RS102221 (2 mg/kg). However, RS102221 did not alter MDMA-induced hyperphagia (for the 1-3 h period) but did exert a stimulant effect, when administered alone, during that period. We have previously shown that MDMA or 5-HT1A/1B receptor agonist RU24969 fails to stimulate locomotor activity in 5-HT1B receptor-null mice. Our present data indicate that the 5-HT2C receptor antagonist RS102221 suppresses MDMA-induced hyperlocomotion. These findings provide the first evidence that the inactivation of 5-HT2C receptors may reduce hypophagia and motor response to MDMA, while a genetic deficit or pharmacological inactivation of 5-HT1B receptors was insufficient to alter the feeding response to MDMA. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/15668722/34_N_methlenedioxymethamphetamine_induced_hypophagia_is_maintained_in_5_HT1B_receptor_knockout_mice_but_suppressed_by_the_5_HT2C_receptor_antagonist_RS102221_ L2 - http://dx.doi.org/10.1038/sj.npp.1300662 DB - PRIME DP - Unbound Medicine ER -