The effect of mephedrone and caffeine, and the influence of WAY-100635 on c-fos expression in the rat brain

Adam, Lucy (2022) The effect of mephedrone and caffeine, and the influence of WAY-100635 on c-fos expression in the rat brain. MRes thesis, University of Nottingham.

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Abstract

Mephedrone is a commonly abused drug, with recreational users comparing its effects to MDMA. Polydrug use of mephedrone has been widely documented and forensic analysis has identified caffeine as key drug that is co-consumed. The current study aimed to identify the changes in c-fos expression, a commonly used marker in research to determine neuronal stimulation in response to mephedrone and caffeine administration, and the effect that inhibition of the 5-HT1A receptor has on this expression.

48 male Lister Hooded rats received i.p. vehicle (saline 1mL/kg) or WAY-100635 (0.5mg/kg) then 30min later vehicle, caffeine (10mg/kg), mephedrone (10mg/kg) or caffeine plus mephedrone (10mg/kg each). Animals were killed using Euthatal and brains were removed to determine c-Fos expression. (This in vivo work was performed by a previous PhD student). Free-floating sections cut coronally at 60μm, and immunohistochemistry was performed.

Mephedrone displayed a main effect in the dorsal striatum, pre-limbic cortex, the nucleus accumbens core and shell. In the shell, the post-hoc tests showed a significant difference between the vehicle + vehicle treatment group and the vehicle + mephedrone treatment groups. When combined with caffeine, there was a main effect observed in the dorsal striatum and the hypothalamus, however no significance was seen between groups using Tukey’s post-hoc tests in either of these regions. In contrast, the post-hoc tests showed a significant increase between the vehicle + vehicle treatment group and the vehicle + mephedrone & caffeine treatment groups observed in the nucleus accumbens shell, core, ventral striatum and pre-limbic cortex. There was no effect of WAY-100635 in any experimental condition.

The results suggest that caffeine displays an additive effect when combined with mephedrone, suggesting it may exacerbate mephedrone induced serotonergic syndrome. Unlike mephedrone alone, the combination of caffeine and mephedrone does not appear to be affected by 5-HT1A receptor antagonism and more work should be completed to investigate the downstream involvement of 5-HT1B, 5-HT2A and dopaminergic receptors.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: King, Madeleine
Fone, Kevin
Keywords: Mephedrone, Caffeine, WAY-100635, c-fos, Rat brain
Subjects: Q Science > QP Physiology > QP501 Animal biochemistry
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 68522
Depositing User: Adam, Lucy
Date Deposited: 31 Jul 2022 04:41
Last Modified: 31 Jul 2022 04:41
URI: http://eprints.nottingham.ac.uk/id/eprint/68522

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