Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia

Shortall, S. E.; Green, A. R.; Swift, K. M.; Fone, K. C.F.; King, M. V.

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 α1-adrenoceptor and dopamine D1 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.

Citation

Shortall, S. E., Green, A. R., Swift, K. M., Fone, K. C., & King, M. V. (2013). Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia. British Journal of Pharmacology, 168(4), 966-977. https://doi.org/10.1111/j.1476-5381.2012.02236.x

• Journal Article Type: Article
• Acceptance Date: Sep 9, 2012
• Online Publication Date: Jan 24, 2013
• Publication Date: 2013-02
• Deposit Date: Jul 4, 2025
• Journal: British Journal of Pharmacology
• Print ISSN: 0007-1188
• Electronic ISSN: 1476-5381
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 168
• Issue: 4
• Pages: 966-977
• DOI: https://doi.org/10.1111/j.1476-5381.2012.02236.x
• Keywords: Cathinone, methcathinone, MDMA, mephedrone, 5-HT, dopamine, plasma noradrenaline, α-adrenoceptors, dopamine receptors, thermoregulation
• Public URL: https://nottingham-repository.worktribe.com/output/3134168
• Publisher URL: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2012.02236.x
• Additional Information: Received: 2012-04-02; Accepted: 2012-09-09; Published: 2013-01-24