Shortall, S.E.
(2015)
Neuropharmacological properties of the cathinones.
PhD thesis, University of Nottingham.
Abstract
At the height of its popularity, mephedrone was the most common recreationally used cathinone. This is thought to be due to its perceived likeness to MDMA. Therefore the aim of this thesis was to examine mephedrone-induced changes in behaviour, body temperature or neurochemistry in the rat and to compare these changes to those observed following MDMA administration. This was achieved by assessing changes in body temperature following acute mephedrone, MDMA, cathinone or methcathinone administration. Additionally, locomotor activity and cognitive tasks were performed following chronic intermittent administration of mephedrone, MDMA or cathinone. These behaviours, as well as mephedrone-induced changes to body temperature and ‘anxiety-related’ behaviour, were also assessed following either pre-treatment with MDMA or co-administration of caffeine. Finally, locomotor activity, body temperature changes and in vivo striatal dopamine release were assessed following rapid repeated dosing of mephedrone, and the roles of dopamine, 5-HT and noradrenaline in these responses were examined. Post mortem monoamine concentrations from specific brain regions were also assessed following acute, chronic intermittent and rapid repeated dosing of mephedrone.
It was found that the neurochemical, behavioural and physiological effects of mephedrone in the rat include hyperactivity, hypothermia, cognitive deficits, anxiety-related behaviour and increased striatal dopamine efflux. Pre-exposure to MDMA, or concomitant caffeine administration, caused an increase in rectal temperature following mephedrone injection while caffeine co-administration prolonged the hyperactive profile of mephedrone. Importantly, unlike MDMA, rapid repeated mephedrone administration (3 x 10 mg kg-1 at 2 h intervals) had no cumulative effect on mephedrone-induced hypothermia or hyperactivity. It is also clear that mephedrone is inducing its effects via noradrenergic, dopaminergic and serotonergic mechanisms. The cathinones and MDMA had varying effects on post mortem tissue levels of the monoamines and their metabolites. Importantly, these effects of mephedrone appear to be occurring by mechanisms that are different, but similar, to MDMA.
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