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Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats.
Drug Alcohol Depend. 2012 Nov 01; 126(1-2):168-75.DA

Abstract

BACKGROUND

Reports from U.S., U.K. and European drug policy entities, and ongoing media accounts, show increasing recreational use of 4-methylmethcathinone (4-MMC, mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV). Severe sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been reported, yet little scientific information is available on the effects of these compounds in laboratory models. Available studies on the neurochemistry of these drugs show that 4-MMC and MDPV enhance DA neurotransmission, while 4-MMC additionally enhances 5-HT neurotransmission--a pattern much like that reported for methamphetamine versus 3,4-methylenedioxymethamphetamine (MDMA). As is the case for designer amphetamines, these neurochemical distinctions may predict differential potential for repetitive versus episodic abuse and distinct lasting toxicities.

METHODS

This study determined relative locomotor stimulant effects of 4-MMC (1-10 mg/kg, s.c.) and MDPV (0.5-5.6 mg/kg, s.c.), in comparison with d-methamphetamine (MA; 0.5-5.6 mg/kg, s.c.) and MDMA (1-7.5 mg/kg, s.c.) on a measure of locomotor activity--voluntary wheel running--in male Wistar rats (N=8).

RESULTS

Compared to counts of wheel rotations after saline, a biphasic change in the pattern of counts was observed after injections of MA and MDPV, with relatively higher counts following lower doses and lower counts following the highest dose. However, monophasic, dose-dependent reductions in counts were observed in response to injections of MDMA and 4-MMC.

CONCLUSION

Thus, voluntary wheel running yielded the same categorical distinctions for these drugs as did prior experiments testing the effects of these drugs on monoaminergic neurotransmission. These data indicate that MDPV produces prototypical locomotor stimulant effects whereas 4-MMC is more similar to the entactogen MDMA.

Authors+Show Affiliations

Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, CA 92037, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22664136

Citation

Huang, Pai-Kai, et al. "Contrasting Effects of D-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone On Wheel Activity in Rats." Drug and Alcohol Dependence, vol. 126, no. 1-2, 2012, pp. 168-75.
Huang PK, Aarde SM, Angrish D, et al. Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Drug Alcohol Depend. 2012;126(1-2):168-75.
Huang, P. K., Aarde, S. M., Angrish, D., Houseknecht, K. L., Dickerson, T. J., & Taffe, M. A. (2012). Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Drug and Alcohol Dependence, 126(1-2), 168-75. https://doi.org/10.1016/j.drugalcdep.2012.05.011
Huang PK, et al. 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. PubMed PMID: 22664136.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. AU - Huang,Pai-Kai, AU - Aarde,Shawn M, AU - Angrish,Deepshikha, AU - Houseknecht,Karen L, AU - Dickerson,Tobin J, AU - Taffe,Michael A, Y1 - 2012/06/03/ PY - 2012/03/14/received PY - 2012/05/10/revised PY - 2012/05/11/accepted PY - 2012/6/6/entrez PY - 2012/6/6/pubmed PY - 2013/4/9/medline SP - 168 EP - 75 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 126 IS - 1-2 N2 - BACKGROUND: Reports from U.S., U.K. and European drug policy entities, and ongoing media accounts, show increasing recreational use of 4-methylmethcathinone (4-MMC, mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV). Severe sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been reported, yet little scientific information is available on the effects of these compounds in laboratory models. Available studies on the neurochemistry of these drugs show that 4-MMC and MDPV enhance DA neurotransmission, while 4-MMC additionally enhances 5-HT neurotransmission--a pattern much like that reported for methamphetamine versus 3,4-methylenedioxymethamphetamine (MDMA). As is the case for designer amphetamines, these neurochemical distinctions may predict differential potential for repetitive versus episodic abuse and distinct lasting toxicities. METHODS: This study determined relative locomotor stimulant effects of 4-MMC (1-10 mg/kg, s.c.) and MDPV (0.5-5.6 mg/kg, s.c.), in comparison with d-methamphetamine (MA; 0.5-5.6 mg/kg, s.c.) and MDMA (1-7.5 mg/kg, s.c.) on a measure of locomotor activity--voluntary wheel running--in male Wistar rats (N=8). RESULTS: Compared to counts of wheel rotations after saline, a biphasic change in the pattern of counts was observed after injections of MA and MDPV, with relatively higher counts following lower doses and lower counts following the highest dose. However, monophasic, dose-dependent reductions in counts were observed in response to injections of MDMA and 4-MMC. CONCLUSION: Thus, voluntary wheel running yielded the same categorical distinctions for these drugs as did prior experiments testing the effects of these drugs on monoaminergic neurotransmission. These data indicate that MDPV produces prototypical locomotor stimulant effects whereas 4-MMC is more similar to the entactogen MDMA. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/22664136/Contrasting_effects_of_d_methamphetamine_34_methylenedioxymethamphetamine_34_methylenedioxypyrovalerone_and_4_methylmethcathinone_on_wheel_activity_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(12)00174-3 DB - PRIME DP - Unbound Medicine ER -