Wheel activity discriminates entactogens from classical stimulants

The following has been accepted for publication:

Huang,P.K., Aarde, S.M., Angrish, D., Houseknecht, K.L., Dickerson, T.J. and Taffe, M.A. Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats, Drug Alcohol Depend, 2012 Nov 1;126(1-2):168-75. doi: 10.1016/j.drugalcdep.2012.05.011. Epub 2012 Jun 3.[PubMed]

In this study, rats were administered doses of methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”), 3,4-methylenedioxypyrovalerone (MDPV, often what is meant by media mentions of “Bath Salts”) and 4-methylmethcathinone (4-MMC or mephedrone) prior to being given the opportunity to run on an activity wheel.

Methamphetamine and MDPV resulted in stimulant-typical inverted U patterns. In other words, the activity was increased at lower to moderate doses and suppressed at higher doses of the drugs.

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.

In contrast, MDMA and 4-MMC produced essentially linear dose-dependent reductions in wheel activity.

The interesting part is that on an open-field or operant box analysis of locomotion, MDMA and 4-MMC each increase activity. As was discussed in that prior blog entry, 4-MMC and MDMA share the neurochemical property of relatively enhanced serotonin response in the nucleus accumbens, an effect which distinguishes these compounds from the classical psychomotor stimulants amphetamine and methamphetamine. Our investigation may have identified a locomotor assay which is better at distinguishing methamphetamine-like from MDMA-like behavioral properties of stimulant drugs.