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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, Madelaine 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

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.

Journal Article Type Article
Publication Date Jul 16, 2015
Journal Addiction Biology
Print ISSN 1355-6215
Electronic ISSN 1355-6215
Publisher Wiley
Peer Reviewed Peer Reviewed
APA6 Citation Shortall, S. E., Spicer, C. H., Ebling, F. J., Green, A. R., Fone, K. C., & King, M. 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, https://doi.org/10.1111/adb.12283
DOI https://doi.org/10.1111/adb.12283
Keywords 5-HT, dopamine, locomotor activity, mephedrone, microdialysis, telemetry
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.nottingh.../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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