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Contribution of monoaminergic mechanisms to the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley rats.
Psychopharmacology (Berl). 2019 Mar; 236(3):963-971.P

Abstract

RATIONALE

3,4-Methylenedioxypyrovalerone (MDPV) is a popular synthetic cathinone reported to have a high abuse potential. Recent preclinical research indicates the psychopharmacology of MDPV is comparable to cocaine. Despite a recent influx of research on the psychopharmacology of MDPV, few studies have employed preclinical drug discrimination methods to discern the neurochemical mechanisms involved in its interoceptive stimulus effects.

OBJECTIVE

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

METHODS

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).

RESULTS

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.

Authors+Show Affiliations

Department of Psychology, Western Michigan University, Kalamazoo, MI, 49008, USA.Department of Psychology, Western Michigan University, Kalamazoo, MI, 49008, USA. lisa.baker@wmich.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30554256

Citation

Risca, Harmony I., and Lisa E. Baker. "Contribution of Monoaminergic Mechanisms to the Discriminative Stimulus Effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley Rats." Psychopharmacology, vol. 236, no. 3, 2019, pp. 963-971.
Risca HI, Baker LE. Contribution of monoaminergic mechanisms to the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley rats. Psychopharmacology (Berl). 2019;236(3):963-971.
Risca, H. I., & Baker, L. E. (2019). Contribution of monoaminergic mechanisms to the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley rats. Psychopharmacology, 236(3), 963-971. https://doi.org/10.1007/s00213-018-5145-8
Risca HI, Baker LE. Contribution of Monoaminergic Mechanisms to the Discriminative Stimulus Effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley Rats. Psychopharmacology (Berl). 2019;236(3):963-971. PubMed PMID: 30554256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of monoaminergic mechanisms to the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley rats. AU - Risca,Harmony I, AU - Baker,Lisa E, Y1 - 2018/12/15/ PY - 2018/05/31/received PY - 2018/12/03/accepted PY - 2020/03/01/pmc-release PY - 2018/12/17/pubmed PY - 2019/10/28/medline PY - 2018/12/17/entrez KW - 3,4-Methylenedioxypyrovalerone KW - Dopamine KW - Drug discrimination KW - Sprague-Dawley rats KW - Synthetic cathinones SP - 963 EP - 971 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 236 IS - 3 N2 - RATIONALE: 3,4-Methylenedioxypyrovalerone (MDPV) is a popular synthetic cathinone reported to have a high abuse potential. Recent preclinical research indicates the psychopharmacology of MDPV is comparable to cocaine. Despite a recent influx of research on the psychopharmacology of MDPV, few studies have employed preclinical drug discrimination methods to discern the neurochemical mechanisms involved in its interoceptive stimulus effects. OBJECTIVE: The aim of this study was to evaluate a variety of monoaminergic agents for substitution, potentiation, or antagonism in rats trained to discriminate MDPV. METHODS: 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). RESULTS: 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/30554256/Contribution_of_monoaminergic_mechanisms_to_the_discriminative_stimulus_effects_of_34_methylenedioxypyrovalerone__MDPV__in_Sprague_Dawley_rats_ L2 - https://dx.doi.org/10.1007/s00213-018-5145-8 DB - PRIME DP - Unbound Medicine ER -