BACKGROUND AND PURPOSE: Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones. EXPERIMENTAL APPROACH: The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines. KEY RESULTS: At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α(1) -adrenoceptor and dopamine D(1) receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists. CONCLUSIONS AND IMPLICATIONS: MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA.
BACKGROUND AND PURPOSE: Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones. EXPERIMENTAL APPROACH: The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines. KEY RESULTS: At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α(1) -adrenoceptor and dopamine D(1) receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists. CONCLUSIONS AND IMPLICATIONS: MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA.
Authors: Adam R Winstock; Luke R Mitcheson; Paolo Deluca; Zoe Davey; Ornella Corazza; Fabrizio Schifano Journal: Addiction Date: 2010-08-23 Impact factor: 6.526
Authors: David M Wood; Susannah Davies; Shaun L Greene; Jenny Button; David W Holt; John Ramsey; Paul I Dargan Journal: Clin Toxicol (Phila) Date: 2010-11 Impact factor: 4.467
Authors: Michael H Baumann; Dorota Zolkowska; Insook Kim; Karl B Scheidweiler; Richard B Rothman; Marilyn A Huestis Journal: Drug Metab Dispos Date: 2009-08-13 Impact factor: 3.922
Authors: Susan M Lantz; Hector Rosas-Hernandez; Elvis Cuevas; Bonnie Robinson; Kenner C Rice; William E Fantegrossi; Syed Z Imam; Merle G Paule; Syed F Ali Journal: Neurosci Lett Date: 2017-07-03 Impact factor: 3.046
Authors: Rui Tao; Ibrahim M Shokry; John J Callanan; H Daniel Adams; Zhiyuan Ma Journal: Psychopharmacology (Berl) Date: 2014-10-11 Impact factor: 4.530
Authors: Nicholas B Miner; Josh S Elmore; Michael H Baumann; Tamara J Phillips; Aaron Janowsky Journal: Neurotoxicology Date: 2017-09-15 Impact factor: 4.294
Authors: Dawn E Muskiewicz; Federico Resendiz-Gutierrez; Omar Issa; F Scott Hall Journal: Pharmacol Biochem Behav Date: 2020-02-12 Impact factor: 3.533
Authors: John H Anneken; Mariana Angoa-Perez; Girish C Sati; David Crich; Donald M Kuhn Journal: Neuropharmacology Date: 2017-08-26 Impact factor: 5.250