Role of serotonin and/or norepinephrine in the MDMA-induced increase in extracellular glucose and glycogenolysis in the rat brain

• Published in: European journal of pharmacology 2010-10, Vol.644 (1-3), p.67-72
• Main Authors: Pachmerhiwala, Rashida, Bhide, Nirmal, Straiko, Megan, Gudelsky, Gary A.
• Format: Article
• Language: English
• Subjects: alpha -Adrenergic receptors; Animals; Biological and medical sciences; Brain; Brain - drug effects; Brain - metabolism; Cortex (prefrontal); Fever - chemically induced; Fluoxetine; Fluoxetine - pharmacology; Glucose; Glucose - metabolism; Glycogen; Glycogenolysis - drug effects; Hippocampus; Hyperthermia; Male; MDMA; Medical sciences; Microdialysis; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Neostriatum; Norepinephrine; Norepinephrine - metabolism; Peripheral blood; Pharmacology. Drug treatments; prazosin; Prazosin - pharmacology; Propranolol; Propranolol - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha - drug effects; Receptors, Adrenergic, alpha - metabolism; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - metabolism; Serotonin; Serotonin - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.07.004

The acute administration of MDMA has been shown to promote glycogenolysis and increase the extracellular concentration of glucose in the striatum. In the present study the role of serotonergic and/or noradrenergic mechanisms in the MDMA-induced increase in extracellular glucose and glycogenolysis was assessed. The relationship of these responses to the hyperthermia produced by MDMA also was examined. The administration of MDMA (10mg/kg, i.p.) resulted in a significant and sustained increase of 65–100% in the extracellular concentration of glucose in the striatum, as well as in the prefrontal cortex and hippocampus, and a 35% decrease in brain glycogen content. Peripheral blood glucose was modestly increased by 32% after MDMA treatment. Treatment of rats with fluoxetine (10mg/kg, i.p.) significantly attenuated the MDMA-induced increase in extracellular glucose in the striatum but had no effect on MDMA-induced glycogenolysis or hyperthermia. Treatment with prazosin (1mg/kg, i.p.) did not alter the glucose or glycogen responses to MDMA but completely suppressed MDMA-induced hyperthermia. Finally, propranolol (3mg/kg, i.p.) significantly attenuated the MDMA-induced increase in extracellular glucose and glycogenolysis but did not alter MDMA-induced hyperthermia. The present results suggest that MDMA increases extracellular glucose in multiple brain regions, and that this response involves both serotonergic and noradrenergic mechanisms. Furthermore, β-adrenergic and α-adrenergic receptors appear to contribute to MDMA-induced glycogenolysis and hyperthermia, respectively. Finally, hyperthermia, glycogenolysis and elevated extracellular glucose appear to be independent, unrelated responses to acute MDMA administration.