Differential effects of cathinone compounds andMDMAon body temperature in the rat, and pharmacological characterization of mephedrone‐induced hypothermia

Mephedrone, a synthetic cathinone, produces different effects on body temperature and brain chemistry than MDMA (ecstasy) in rats. MDMA caused sustained decreases in rectal and tail temperature, while mephedrone caused only a transient drop in rectal temperature and a prolonged decrease in tail temperature. In contrast, cathinone and methcathinone raised rectal temperature. MDMA reduced serotonin and certain metabolites in several brain regions, whereas cathinone and methcathinone increased the dopamine metabolite homovanillic acid and serotonin metabolite 5-HIAA in the striatum. Mephedrone increased plasma noradrenaline, which was blocked by certain receptor antagonists. The adverse effects of cathinones in humans cannot be extrapolated from MDMA data.

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Abstract

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 .