Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats.
Sinead E Shortall, Alfred Richard Green, Kevin Cf Fone, Madeleine V. King
Journal of Psychopharmacology July 2016 DOI: 10.1177/0269881116650408 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Mephedrone Caffeine |
| Dose | 10 mg/kg mephedrone, 10 mg/kg caffeine |
| Duration | Twice weekly on consecutive days for three weeks, with assessments on days 1, 2, 8, 9, 15, and 16, and brain collection seven days after the final injection |
| Measures | Locomotor activity, novel object discrimination (NOD), elevated plus maze (EPM), rectal temperature, pre-pulse inhibition (PPI) of acoustic startle response, 5-hydroxytryptamine (5-HT), dopamine and their metabolites |
| Topics | Anxiety |
| Keywords | Mephedrone Body temperature Caffeine Locomotor activity |
| Key findings | Caffeine combined with mephedrone enhanced locomotor activity beyond either drug alone and converted mephedrone-induced hypothermia to hyperthermia, while abolishing mephedrone's anxiogenic effect on the elevated plus maze; no long-term neurotoxicity was detected. The authors suggest this combination may be dangerous and that polydrug use should be considered in recreational drug research. |
Abstract
Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs.
Comparable studies
Other preclinical and animal studies on anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Chronic, Intermittent Microdoses of the Psychedelic N , N -Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents Male rats | 2019 | Animal study | |
| 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Mice | 2015 | Preclinical experimental study | |
| Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline Male mice exposed to chronic restraint stress | 2022 | Preclinical experimental study |
Citations in the library
Cited by 2
- Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats Frontiers in Psychiatry November 17, 2017
- Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine. Pharmacology, Biochemistry, and Behavior April 2020
Cites 17
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- The preclinical pharmacology of mephedrone; not justMDMAby another name British Journal of Pharmacology March 24, 2014
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- Differential effects of cathinone compounds andMDMAon body temperature in the rat, and pharmacological characterization of mephedrone‐induced hypothermia British Journal of Pharmacology October 8, 2012
and 12 more in the library