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

Shortall, Sinead E.; Spicer, Clare H.; Ebling, Francis J.P.; Green, A. Richard; Fone, Kevin C.F.; King, Madeleine V.

Authors

Sinead E. Shortall sinead.shortall@nottingham.ac.uk

Clare H. Spicer clare.spicer@nottingham.ac.uk

Francis J.P. Ebling fran.ebling@nottingham.ac.uk

A. Richard Green richard.green@nottingham.ac.uk

KEVIN FONE KEVIN.FONE@NOTTINGHAM.AC.UK
Professor of Neuroscience



Abstract

© 2015 Society for the Study of Addiction The psychoactive effects of mephedrone are commonly compared with those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action, users often employ repeated administration to maintain its psychoactive effects. 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 (1 ml/kg, i.p.) or mephedrone HCl (10 mg/kg) at 2 h 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 (150 µg) or 6-hydroxydopamine (300 µg) 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 (−30 min) with the 5-HT 1A receptor antagonist WAY-100635 (0.5 mg/kg), 5-HT 1B receptor antagonist GR 127935 (3 mg/kg) or the 5-HT 7 receptor antagonist SB-258719 (10 mg/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-HT 1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT 1A 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-HT 1B and 5-HT 1A receptors.

Citation

Shortall, S. E., Spicer, C. H., Ebling, F. J., Green, A. R., Fone, K. C., & King, M. V. (2016). Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone. Addiction Biology, 21(6), 1127-1139. https://doi.org/10.1111/adb.12283

Journal Article Type Article
Acceptance Date Jun 12, 2015
Online Publication Date Jul 16, 2015
Publication Date Nov 1, 2016
Deposit Date Sep 21, 2015
Publicly Available Date Sep 21, 2015
Journal Addiction Biology
Print ISSN 1355-6215
Electronic ISSN 1369-1600
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 21
Issue 6
Pages 1127-1139
DOI https://doi.org/10.1111/adb.12283
Keywords 5-HT, dopamine, locomotor activity, mephedrone, microdialysis, telemetry
Public URL http://eprints.nottingham.ac.uk/id/eprint/30185
Publisher URL http://onlinelibrary.wiley.com/doi/10.1111/adb.12283/abstract
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf

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Shortall 2015 AddictionBio.pdf (377 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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