TL neuro

April 4, 2013

3,4-methylenedioxypyrovalerone (MDPV, “bath salts”): A potent reinforcer with significant abuse liability

Filed under: Cathinones, IVSA, MDPV — mtaffe @ 11:46 am

The following paper has been accepted for publication:

Aarde, S.M., Huang, P-K, Creehan, K.M., Dickerson, T.J. and Taffe, M.A. The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats. Neuropharmacology, 2013, 71:130-140. [ PubMed ][ PublisherSite ]

In this paper we contrast the novel substituted cathinone drug MDPV (apparently the most common “bath salt” in the US to date) with the better-known drug of abuse, d-methamphetamine (MA). For these studies we examined intravenous self-administration in male Wistar rats which were previously trained to complete a Fixed Ratio of 5 presses to obtain a food pellet reward. After exhibiting stable response rates for food, groups were switched to intravenous delivery of MDPV or MA (0.05 mg/kg/inf for either drug) as the reinforcer.

We show that rats will maintain stable levels of responding for drug within 10 sessions and that approximately twice as many infusion of MDPV are self-administered compared with MA under these conditions. We then went on to do a dose-substitution manipulation in which the available per-infusion dose was varied across sessions, first under FR5 conditions and then using a Progressive Ratio (PR) procedure.

Aarde13-MDPV-PR2In a PR approach, each successive reinforcer within the session requires more lever pressing to obtain than did the prior one. The idea is that as the amount of “work” required for each dose goes up, the animal will eventually quit responding. In this figure, reproduced from the paper, it is shown that the amount of pressing depends on dose and that rats will emit far more lever presses for MDPV than for MA. The ascending/descending curves were approximately superimposed in terms of the per-infusion dose for both compounds, this is typically interpreted as the drugs having similar potency. The relatively greater amount of lever responding (and therefore infusions obtained) is typically interpreted as greater efficacy of MDPV relative to MA. The only prior study of MDPV self-administration in a rat model (Watterson et al, in press) only compared one dose of MA to a narrower range of MDPV doses so it was not possible to make an extensive comparison from that study.

The paper also compared the locomotor and body temperature effects of acute bolus challenge with MDPV and MA. We found a similar propensity of MDPV and MA to increase home cage locomotion with a stimulant-typical inverted-U dose-response function (1.0 mg/kg, s.c. most effective for both drugs). This finding was similar to our prior report on exercise wheel activity (Huang et al, 2012). We found very little modulation of body temperature after MDPV administration; this lack of effect contrasts with hyperthermia reported in a mouse model by Fantegrossi and colleagues. Additional work will be required to understand if this is a matter of the doses used, the species in question or possibly the ambient temperature under which the studies were conducted.

Finally, we show that MDPV induces repetitive, stereotyped behavior in a dose-dependent manner under both acute-challenge and self-administration conditions.

The paper demonstrates that MDPV is a prototypical psychomotor stimulant. It is potently reinforcing in a self-administration model of compulsive use, stimulates locomotor activity at moderate doses and induces repetitive, stereotyped behavior after higher doses. In these studies MDPV is about equi-potent with MA but is much more efficacious in the self-administration paradigm. Thus these data support a conclusion that MDPV poses a risk for uncontrolled use and dependence that is even greater than that of MA.

Additional Reading:

TLNeuro blog posts on MDPV

Watterson et al. 2012 Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV).

Baumann et al. 2013 Powerful cocaine-like actions of 3,4-Methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products.

Fantegrossi et al. 2013 In vivo effects of abused ‘bath salt’ constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: drug discrimination, thermoregulation, and locomotor activity.

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