Role of the serotonin 5-HT(2A) receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine
by
Herin DV, Liu S, Ullrich T, Rice KC, Cunningham KA.
Department of Pharmacology and Toxicology,
Center for Addiction Research, University of Texas Medical Branch,
Galveston, TX 77555-1031, USA,
kcunning@utmb.edu.
Psychopharmacology (Berl). 2005 Apr;178(4):505-13


ABSTRACT

RATIONALE: Contradictory evidence exists regarding the role of the 5-HT(2A) receptor (5-HT(2A)R) in hyperactivity and hyperthermia elicited by the substituted amphetamine (+)-3,4-methylenedioxymethamphetamine.OBJECTIVES: The present studies examined the ability of the selective 5-HT(2A)R antagonist M100907 to block hyperactivity and hyperthermia produced across the (+)-MDMA dose-effect curve.METHODS: Male rats were pretreated with M100907 (0, 0.25, 0.5, 1, and 2 mg/kg) followed by treatment with (+)-MDMA (0-12 mg/kg); activity was recorded for 90 min followed by determination of rectal temperature. Additionally, we investigated the ability of M100907 (0 and 0.5 mg/kg) to reverse hyperthermia elicited by (+)-MDMA (12 mg/kg).RESULTS: The first study demonstrated that M100907 attenuated hyperactivity in the periphery of the monitor and eliminated rearing induced by (+)-MDMA (3 mg/kg) with no effect on basal activity. In two subsequent studies, (+)-MDMA (0-12 mg/kg) dose-dependently increased peripheral activity and rearing and produced hyperthermia. Pretreatment with M100907 decreased peripheral activity evoked by (+)-MDMA, right-shifted the dose-effect curve for rearing, and blocked (+)-MDMA-induced hyperthermia, while having no effect when administered alone. A final study demonstrated the ability of M100907 (0.5 mg/kg) to reverse hyperthermia produced by (+)-MDMA (12 mg/kg).CONCLUSIONS: These results suggest that the 5-HT(2A)R contributes to the generation of peripheral hyperactivity and rearing and, especially, the hyperthermia evoked by (+)-MDMA and that 5-HT(2A)R antagonists should be further investigated as treatments for the psychological and hyperthermic effects of (+/-)-MDMA.

5-HT1a
5-HT1b
5-HT2a
5-HT2b
5-HT2c
History
Ketanserin
MDMA/MDE
Controversies
Protect and survive
Ecstasy and tryptophan
Ecstasy and serotonin synthesis


Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family