Contribution of monoaminergic mechanisms to the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley rats

These findings indicate MDPV's interoceptive stimulus effects are mediated predominantly by dopaminergic actions, although serotonergic and/or noradrenergic modulation of these effects cannot be ruled out. Further investigations into the neurochemical actions involved in the discriminative stimulus effects of MDPV may serve to inform medication discovery and development for the treatment of MDPV abuse.

Male Sprague-Dawley rats were trained to discriminate 0.5 (experiment 1) or 1 mg/kg MDPV (experiment 2) from saline under an FR 20 schedule of food reinforcement. In experiment 1, MDMA, MDA, and their respective optical isomers (0.75-3 mg/kg), cocaine (2.5-20 mg/kg), GBR 12909 (5-40 mg/kg), and desipramine (3.2-10 mg/kg) were assessed for substitution. GBR 12909 (40 mg/kg) and desipramine (3.2 mg/kg) were subsequently assessed for potentiation of the MDPV cue. In experiment 2, stimulus antagonism tests were conducted with dopamine antagonists (Sch 23390, haloperidol) and serotonin antagonists (pirenperone, MDL100907, WAY 100635).

The aim of this study was to evaluate a variety of monoaminergic agents for substitution, potentiation, or antagonism in rats trained to discriminate MDPV.

The MDMA and MDA enantiomers produced divergent results, with virtually no substitution by (-)-MDMA or (-)-MDA, partial substitution with (+)-MDA, and full substitution with (+)-MDMA, as well as full substitution by the racemates, (±)-MDMA and (±)-MDA. Consistent with previous findings, cocaine fully substituted for MDPV. Although no dose of GBR 12909 or desipramine substituted for MDPV, these reuptake inhibitors enhanced the discriminative stimulus effects of lower MDPV doses. Both D1 (Sch 23390) and D2 (haloperidol) DA antagonists attenuated 1 mg/kg MDPV discrimination, whereas none of the 5-HT antagonists assessed altered MDPV discrimination. Conclusions: These findings indicate MDPV's interoceptive stimulus effects are mediated predominantly by dopaminergic actions, although serotonergic and/or noradrenergic modulation of these effects cannot be ruled out. Further investigations into the neurochemical actions involved in the discriminative stimulus effects of MDPV may serve to inform medication discovery and development for the treatment of MDPV abuse.