Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats - PubMed (original) (raw)

Comparative Study

Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats

Pai-Kai Huang et al. Drug Alcohol Depend. 2012.

Abstract

Background: Reports from U.S., U.K. and European drug policy entities, and ongoing media accounts, show increasing recreational use of 4-methylmethcathinone (4-MMC, mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV). Severe sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been reported, yet little scientific information is available on the effects of these compounds in laboratory models. Available studies on the neurochemistry of these drugs show that 4-MMC and MDPV enhance DA neurotransmission, while 4-MMC additionally enhances 5-HT neurotransmission--a pattern much like that reported for methamphetamine versus 3,4-methylenedioxymethamphetamine (MDMA). As is the case for designer amphetamines, these neurochemical distinctions may predict differential potential for repetitive versus episodic abuse and distinct lasting toxicities.

Methods: This study determined relative locomotor stimulant effects of 4-MMC (1-10 mg/kg, s.c.) and MDPV (0.5-5.6 mg/kg, s.c.), in comparison with d-methamphetamine (MA; 0.5-5.6 mg/kg, s.c.) and MDMA (1-7.5 mg/kg, s.c.) on a measure of locomotor activity--voluntary wheel running--in male Wistar rats (N=8).

Results: Compared to counts of wheel rotations after saline, a biphasic change in the pattern of counts was observed after injections of MA and MDPV, with relatively higher counts following lower doses and lower counts following the highest dose. However, monophasic, dose-dependent reductions in counts were observed in response to injections of MDMA and 4-MMC.

Conclusion: Thus, voluntary wheel running yielded the same categorical distinctions for these drugs as did prior experiments testing the effects of these drugs on monoaminergic neurotransmission. These data indicate that MDPV produces prototypical locomotor stimulant effects whereas 4-MMC is more similar to the entactogen MDMA.

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Figures

Fig. 1

Mean counts of wheel rotations after injections of d-methamphetamine (MA; N = 8): a) Effect of injection dose on mean _binned_-counts (5-min intervals) as a function of time bin. b) Effect of time-from-injection on mean _binned_-counts as a function of injection dose. c) Effect of injection dose on mean _total_-counts (i.e., sum of the twelve _binned_-counts). For the effect of dose, symbols over bars indicate a mean difference from vehicle (*) or from 1.0 mg/kg (@). For the effect of time-from-injection, symbols over bars indicate a mean difference from the 5-min bin (α), from the 10-min bin (β) or from the 15-min bin (λ). Error bars represent SEM.

Fig. 2

Mean counts of wheel rotations after injections of 3,4-methylenedioxymethamphetamine (MDMA; N = 8): a) Effect of injection dose on mean _binned_-counts (5-min intervals) as a function of time bin. b) Effect of time-from-injection on mean _binned_-counts as a function of injection dose. c) Effect of injection dose on mean _total_-counts (i.e., sum of the twelve _binned_-counts). For the effect of dose, symbols over bars indicate a mean difference from vehicle (*) or from 1.0 mg/kg (#). For the effect of time-from-injection, symbols over bars indicate a mean difference from the 5-min bin (α). Error bars represent SEM.

Fig. 3

Mean counts of wheel rotations after injections of 3,4-methylenedioxypyrovalerone (MDPV; N = 8): a) Effect of injection dose on mean _binned_-counts (5-min intervals) as a function of time bin. b) Effect of time-from-injection on mean _binned_-counts as a function of injection dose. c) Effect of injection dose on mean _total_-counts (i.e., sum of the twelve _binned_-counts). For the effect of dose, symbols over bars indicate a mean difference from vehicle (*), from 0.5 mg/kg (#) or from 1.0 mg/kg (@). For the effect of time-from-injection, symbols over bars indicate a mean difference from the 5-min bin (α) or from the 10-min bin (β). Error bars represent SEM.

Fig. 4

Mean counts of wheel rotations after injections of 4-methylmethcathinone (4-MMC; N = 8): a) Effect of injection dose on mean _binned_-counts (5-min intervals) as a function of time bin. b) Effect of time-from-injection on mean _binned_-counts as a function of injection dose. c) Effect of injection dose on mean _total_-counts (i.e., sum of the twelve _binned_-counts). For the effect of dose, symbols over bars indicate a mean difference from vehicle (*) or from 1.0 mg/kg (#). For the effect of time-from-injection, symbols over bars indicate a mean difference from the 5-min bin (α). Error bars represent SEM.

Fig. 5

Mean counts of wheel rotations after injections of vehicle only for each treatment block (Tx Block; N = 8): a) Effect of Tx Block on mean _binned_-counts (5-min intervals) as a function of time bin. b) Effect of time-from-injection on mean _binned_-counts as a function of Tx Block. c) Effect of Tx Block on mean _total_-counts (i.e., sum of the twelve _binned_-counts). Means did not differ as a function of Tx Block for either _binned_-counts or _total_-counts. For the effect of time-from-injection, symbols over bars indicate a mean difference from the 5-min bin (α). Error bars represent SEM.

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Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats - PubMed (original) (raw)