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, 7 (8), e44652

Effect of Ambient Temperature on the Thermoregulatory and Locomotor Stimulant Effects of 4-methylmethcathinone in Wistar and Sprague-Dawley Rats

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Effect of Ambient Temperature on the Thermoregulatory and Locomotor Stimulant Effects of 4-methylmethcathinone in Wistar and Sprague-Dawley Rats

M Jerry Wright Jr et al. PLoS One.

Abstract

The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, "plant food", "bath salts") is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1-10 mg/kg ) using an implantable radiotelemetry system under conditions of low (23°C) and high (27°C) ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1(A/7) receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA.

Conflict of interest statement

Competing Interests: The co-author MAT is a PLoS ONE Editorial Board member. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Mean (N = 8; ± SEM) body temperature and activity rates (count/min) are presented by the 5 minute sampling interval for Wistar and Sprague-Dawley rats following challenge with 4-MMC (1.0–10.0 mg/kg, s.c.) and vehicle under 23°C and 27°C TA conditions.
Figure 2
Figure 2. Statistical analysis was conducted on hourly bins (mean temperature and summed activity counts) for three hours after injection.
Post-hoc confirmation of a significant difference from the following conditions is indicated by: Vehicle condition at a given timepoint: †; Pretreatment value within dose condition: §; Pretreatment baseline and vehicle condition at that time point: #; Vehicle condition, pretreatment value and between strains: *; Pretreatment value and between strains: &; Vehicle condition at the respective timepoint and between strains: ‡; Between strains: @.
Figure 3
Figure 3. Mean (± SEM) body temperature and activity data are presented for Wistar (N = 7) and Sprague-Dawley (N = 8) rats following challenge with vehicle, d-methamphetamine (1.0, 5.6 mg/kg, s.c.) and 4-MMC (3.2, 10.0 mg/kg, s.c.) under 23°C TA.
Data were collected at 5 minute intervals (upper panels) and were statistically analyzed as hourly averages. All other statistical conventions are as outlined in Figure 2.
Figure 4
Figure 4. Mean (± SEM) body temperature is presented for Wistar (N = 7) and Sprague-Dawley (N = 7) rats following challenge with 8-OH-DPAT under 23°C TA conditions.
Data were collected at 5 minute intervals (upper panels) and are analyzed as hourly averages (lower panels). A reliable difference between strains (only) is indicated by %; all other statistical conventions are as outlined in Figure 2.
Figure 5
Figure 5. Mean (N = 3, ±SEM) plasma levels of 4-MMC up to 6 hrs after administration of 5.6 mg/kg 4-MMC, s.c.
Figure 6
Figure 6. Serotonin and Dopamine levels in the nucleus accumbens (shell) region following 10 mg/kg 4-MMC, s.c. (N = 5, ±SEM).
Open symbols indicate significant change from baseline.

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