Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat

Shortall, Sinead E.; Macerola, Alice E.; Swaby, Rabbi; Jayson, Rebecca; Korsah, Chantal; Pillidge, Katharine; Wigmore, Peter; Ebling, Francis J. P.; Green, A. Richard; Fone, Kevin C. F.; King, Madeleine V.

doi:10.1016/j.euroneuro.2012.09.005

Cited by 75 publications

(111 citation statements)

References 44 publications

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“…The predominant locomotor stimulant effect of mephedrone in vehicle pre-treated rats was a prolonged increase in ambulatory activity (p<0.05-0.001, accompanied by a smaller increase in fine movement without increased rearing consistent with previous studies by our group (Shortall et al, 2013b) and the current telemetry data. It was briefly attenuated WAY-100653 (Fig.…”

Section: Locomotor Activitysupporting

confidence: 81%

“…Locomotor activity (LMA) and rectal temperature were recorded from separate groups to establish the role of specific 5-HT receptors in acute mephedrone-induced hyperactivity and hypothermia, using previously described methods (Shortall et al, 2013a;Shortall et al, 2013b). Rats (n=8 per treatment group) received saline vehicle (1ml/kg, i.p.…”

Section: Neurochemical Detection By High Performance Liquid Chromatogmentioning

confidence: 99%

“…injection), rats were killed by concussion followed by immediate decapitation, and the hypothalamus, right striatum, frontal cortex and hippocampus were collected on a refrigerated table (4°C), flash frozen in liquid nitrogen and stored at -80°C until analysis of dopamine, 5-HT and their major metabolites by high performance liquid chromatography-electrical detection, as previously described (Shortall et al, 2013b). Samples were thawed, weighed and sonicated for 30s in 800µl 0.05M perchloric acid containing 1µM sodium metabisulphite, centrifuged (17400xg, 4°C for 20min; Harrier 18/80: MSE Scientific Instruments, London, UK) and the supernatant filtered (0.45µM syringe tip filter, Kinesis Ltd, Saint Neots, UK).…”

Section: Neurochemical Detection By High Performance Liquid Chromatogmentioning

confidence: 99%

“…Importantly, 10mg/kg i.p. produces robust but sub-maximal physiological and behavioral changes in the rat (Shortall et al, 2013a;Shortall et al, 2013b;Wright et al, 2012), thereby enabling detection of either enhanced or attenuated temperature and locomotor effects following repeated injection (Green et al, 2014). In the current study, all experiments were performed at ambient temperature as Wright et al, (2012) observed that mephedrone produced a comparable hypothermia and increase in locomotor activity when recorded at normal (23 o C) and elevated (27 o C) ambient room temperature in Wistar rats.…”

Section: Introductionmentioning

confidence: 99%

“…Because mephedrone causes hyperlocomotion (Shortall et al, 2013b) and the striatum plays a role in motor activity (Schultz, 2000), extracellular dopamine and 5-HT efflux from this region were measured by in vivo microdialysis to examine whether neurotransmitter release correlated with the behavioral effects.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2015

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. (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 1355-6215Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/30185/1/Shortall%202015%20AddictionBio.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the University of Nottingham End User licence and may be reused according to the conditions of the licence. For more details see: http://eprints.nottingham.ac.uk/end_user_agreement.pdf A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.

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Section: Locomotor Activitysupporting

confidence: 81%

Section: Neurochemical Detection By High Performance Liquid Chromatogmentioning

confidence: 99%

Section: Neurochemical Detection By High Performance Liquid Chromatogmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2015

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The psychoactive cathinone derivative pyrovalerone alters locomotor activity and decreases dopamine receptor expression in zebrafish (Danio rerio)

et al. 2019

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IntroductionPyrovalerone (4‐methyl‐β‐keto‐prolintane) is a synthetic cathinone (beta‐keto‐amphetamine) derivative. Cathinones are a concern as drugs of abuse, as related street drugs such as methylenedioxypyrovalerone have garnered significant attention. The primary mechanism of action of cathinones is to inhibit reuptake transporters (dopamine and norepinephrine) in reward centers of the central nervous system.MethodsWe measured bioenergetic, behavioral, and molecular responses to pyrovalerone (nM‐µM) in zebrafish to evaluate its potential for neurotoxicity and neurological impairment.ResultsPyrovalerone did not induce any mortality in zebrafish larvae over a 3‐ and 24‐hr period; however, seizures were prevalent at the highest dose tested (100 µM). Oxidative phosphorylation was not affected in the embryos, and there was no change in superoxide dismutase 1 expression. Following a 3‐hr treatment to pyrovalerone (1–100 µM), larval zebrafish (6d) showed a dose‐dependent decrease (70%–90%) in total distance moved in a visual motor response (VMR) test. We interrogated potential mechanisms related to the hypoactivity, focusing on the expression of dopamine‐related transcripts as cathinones can modulate the dopamine system. Pyrovalerone decreased the expression levels of dopamine receptor D1 (~60%) in larval zebrafish but did not affect the expression of tyrosine hydroxylase, dopamine active transporter, or any other dopamine receptor subunit examined, suggesting that pyrovalerone may regulate the expression of dopamine receptors in a specific manner.DiscussionFurther studies using zebrafish are expected to reveal new insight into molecular mechanisms and behavioral responses to cathinone derivates, and zebrafish may be a useful model for understanding the relationship between the dopamine system and bath salts.

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Neuropharmacology of Synthetic Cathinones

Baumann

Walters

Niello

et al. 2018

Handbook of Experimental Pharmacology

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Synthetic cathinones are derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant Catha edulis. Cathinone is the β-keto analog of amphetamine, and all synthetic cathinones display a β-keto moiety in their structure. Several synthetic cathinones are widely prescribed medications (e.g., bupropion, Wellbutrin®), while others are problematic drugs of abuse (e.g., 4-methylmethcathinone, mephedrone). Similar to amphetamines, synthetic cathinones are psychomotor stimulants that exert their effects by impairing the normal function of plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and 5-HT (SERT). Ring-substituted cathinones like mephedrone are transporter substrates that evoke neurotransmitter release by reversing the normal direction of transporter flux (i.e., releasers), whereas pyrrolidine-containing cathinones like 3,4methylenedioxypyrovalerone (MDPV) are potent transporter inhibitors that block neurotransmitter uptake (i.e., blockers). Regardless of molecular mechanism, all synthetic cathinones increase extracellular monoamine concentrations in the brain, thereby enhancing cell-to-cell monoamine signaling. Here, we briefly review the mechanisms of action, structure-activity relationships, and in vivo pharmacology of synthetic cathinones. Overall, the findings show that certain synthetic cathinones are powerful drugs of abuse that could pose significant risk to users.

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Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat

Cited by 75 publications

References 44 publications

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

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

The psychoactive cathinone derivative pyrovalerone alters locomotor activity and decreases dopamine receptor expression in zebrafish (Danio rerio)

Neuropharmacology of Synthetic Cathinones

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