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Sensitization to the locomotor stimulant effects of "bath salt" constituents, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in male Sprague-Dawley rats.
Drug Alcohol Depend. 2016 Jul 01; 164:128-134.DA

Abstract

BACKGROUND

Synthetic cathinones, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), serve as a substrate or blocker at monoaminergic transporters, respectively, and produce locomotor stimulant effects in rodents. The present study investigated in rats the effects of repeated exposure to 4-MMC, MDPV, or mixtures of the two on the induction of locomotor sensitization and expression of cross-sensitization to cocaine.

METHODS

Seventy-two male Sprague-Dawley rats received daily intraperitoneal injections of saline, MDPV (0.5mg/kg), 4-MMC (0.5, 1.0, or 2.0mg/kg) or mixtures of 0.5mg/kg MDPV+4-MMC (0.5, 1.0, or 2.0mg/kg) for seven consecutive days. Locomotor activity was recorded on days 1 and 7 and again after an acute injection of 5mg/kg cocaine following a 10day drug washout period.

RESULTS

Rats injected with 0.5mg/kg MDPV, 0.5, 1.0, or 2.0mg/kg 4-MMC, or 2.0mg/kg 4-MMC+0.5mg/kg MDPV displayed time-dependent increases in horizontal activity that were augmented on day 7 compared to day 1. In addition, rats pretreated with 0.5mg/kg MDPV, 2.0mg/kg 4-MMC, or mixtures of 4-MMC+MDPV displayed an enhanced response to cocaine.

CONCLUSIONS

Locomotor responses sensitize to MDPV and to certain mixtures of MDPV and 4-MMC following repeated dosing. Furthermore, previous exposure to these substances may produce cross-sensitization to the locomotor stimulant effects of cocaine. Considered together with recent findings that 4-MMC and MDPV have different sites of action, but both influence monoaminergic functioning, further investigations utilizing a variety of behavioral assays may prove informative regarding the abuse liability of synthetic cathinone mixtures.

Authors+Show Affiliations

Department of Psychology, Western Michigan University, Kalamazoo, MI, United States.Department of Psychology, Western Michigan University, Kalamazoo, MI, United States.Department of Psychology, Western Michigan University, Kalamazoo, MI, United States.Department of Psychology, Western Michigan University, Kalamazoo, MI, United States. Electronic address: lisa.baker@wmich.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27181413

Citation

Berquist, Michael D., et al. "Sensitization to the Locomotor Stimulant Effects of "bath Salt" Constituents, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in Male Sprague-Dawley Rats." Drug and Alcohol Dependence, vol. 164, 2016, pp. 128-134.
Berquist MD, Traxler HK, Mahler AM, et al. Sensitization to the locomotor stimulant effects of "bath salt" constituents, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in male Sprague-Dawley rats. Drug Alcohol Depend. 2016;164:128-134.
Berquist, M. D., Traxler, H. K., Mahler, A. M., & Baker, L. E. (2016). Sensitization to the locomotor stimulant effects of "bath salt" constituents, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in male Sprague-Dawley rats. Drug and Alcohol Dependence, 164, 128-134. https://doi.org/10.1016/j.drugalcdep.2016.05.001
Berquist MD, et al. Sensitization to the Locomotor Stimulant Effects of "bath Salt" Constituents, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in Male Sprague-Dawley Rats. Drug Alcohol Depend. 2016 Jul 1;164:128-134. PubMed PMID: 27181413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitization to the locomotor stimulant effects of "bath salt" constituents, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in male Sprague-Dawley rats. AU - Berquist,Michael D,2nd AU - Traxler,Haily K, AU - Mahler,Alyssa M, AU - Baker,Lisa E, Y1 - 2016/05/09/ PY - 2016/01/29/received PY - 2016/04/27/revised PY - 2016/05/02/accepted PY - 2016/5/17/entrez PY - 2016/5/18/pubmed PY - 2017/10/17/medline KW - 3,4- KW - 4-MMC KW - 4-Methylmethcathinone KW - Bath salts KW - Cocaine KW - Cross-sensitization< KW - Locomotor sensitization KW - MDPV KW - Mephedrone KW - Methylenedioxypyrovalerone KW - Rats KW - Synthetic cathinones SP - 128 EP - 134 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 164 N2 - BACKGROUND: Synthetic cathinones, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), serve as a substrate or blocker at monoaminergic transporters, respectively, and produce locomotor stimulant effects in rodents. The present study investigated in rats the effects of repeated exposure to 4-MMC, MDPV, or mixtures of the two on the induction of locomotor sensitization and expression of cross-sensitization to cocaine. METHODS: Seventy-two male Sprague-Dawley rats received daily intraperitoneal injections of saline, MDPV (0.5mg/kg), 4-MMC (0.5, 1.0, or 2.0mg/kg) or mixtures of 0.5mg/kg MDPV+4-MMC (0.5, 1.0, or 2.0mg/kg) for seven consecutive days. Locomotor activity was recorded on days 1 and 7 and again after an acute injection of 5mg/kg cocaine following a 10day drug washout period. RESULTS: Rats injected with 0.5mg/kg MDPV, 0.5, 1.0, or 2.0mg/kg 4-MMC, or 2.0mg/kg 4-MMC+0.5mg/kg MDPV displayed time-dependent increases in horizontal activity that were augmented on day 7 compared to day 1. In addition, rats pretreated with 0.5mg/kg MDPV, 2.0mg/kg 4-MMC, or mixtures of 4-MMC+MDPV displayed an enhanced response to cocaine. CONCLUSIONS: Locomotor responses sensitize to MDPV and to certain mixtures of MDPV and 4-MMC following repeated dosing. Furthermore, previous exposure to these substances may produce cross-sensitization to the locomotor stimulant effects of cocaine. Considered together with recent findings that 4-MMC and MDPV have different sites of action, but both influence monoaminergic functioning, further investigations utilizing a variety of behavioral assays may prove informative regarding the abuse liability of synthetic cathinone mixtures. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/27181413/Sensitization_to_the_locomotor_stimulant_effects_of_"bath_salt"_constituents_4_methylmethcathinone__4_MMC__and_34_methylenedioxypyrovalerone__MDPV__in_male_Sprague_Dawley_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(16)30077-1 DB - PRIME DP - Unbound Medicine ER -