Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

Shortall, Sinead E. and Spicer, Clare H. and Ebling, Francis J.P. and Green, A. Richard and Fone, Kevin C.F. and King, Madelaine V. (2015) Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone. Addiction Biology . ISSN 1355-6215

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Abstract

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors.

Item Type: Article
Keywords: 5-HT, dopamine, locomotor activity, mephedrone, microdialysis, telemetry
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Biomedical Sciences
Identification Number: https://doi.org/10.1111/adb.12283
Depositing User: Shortall, Sinead
Date Deposited: 21 Sep 2015 08:14
Last Modified: 14 Sep 2016 21:37
URI: http://eprints.nottingham.ac.uk/id/eprint/30185

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