Tags

Type your tag names separated by a space and hit enter

Reinforcing and neurochemical effects of the "bath salts" constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats.
Psychopharmacology (Berl). 2016 05; 233(10):1981-90.P

Abstract

RATIONALE

3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called "bath salts" products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT).

OBJECTIVES

We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV.

METHODS

To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats.

RESULTS

MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. In contrast, methylone self-administration (0.3 and 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT.

CONCLUSIONS

Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats, suggesting these drugs possess significant abuse liability in humans.

Authors+Show Affiliations

Preclinical Pharmacology Section, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA. cschind@helix.nih.gov.Preclinical Pharmacology Section, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.Preclinical Pharmacology Section, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.Designer Drug Research Unit, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53706, USA.School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.Designer Drug Research Unit, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

26319160

Citation

Schindler, Charles W., et al. "Reinforcing and Neurochemical Effects of the "bath Salts" Constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in Male Rats." Psychopharmacology, vol. 233, no. 10, 2016, pp. 1981-90.
Schindler CW, Thorndike EB, Goldberg SR, et al. Reinforcing and neurochemical effects of the "bath salts" constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats. Psychopharmacology (Berl). 2016;233(10):1981-90.
Schindler, C. W., Thorndike, E. B., Goldberg, S. R., Lehner, K. R., Cozzi, N. V., Brandt, S. D., & Baumann, M. H. (2016). Reinforcing and neurochemical effects of the "bath salts" constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats. Psychopharmacology, 233(10), 1981-90. https://doi.org/10.1007/s00213-015-4057-0
Schindler CW, et al. Reinforcing and Neurochemical Effects of the "bath Salts" Constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in Male Rats. Psychopharmacology (Berl). 2016;233(10):1981-90. PubMed PMID: 26319160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reinforcing and neurochemical effects of the "bath salts" constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats. AU - Schindler,Charles W, AU - Thorndike,Eric B, AU - Goldberg,Steven R, AU - Lehner,Kurt R, AU - Cozzi,Nicholas V, AU - Brandt,Simon D, AU - Baumann,Michael H, Y1 - 2015/08/29/ PY - 2015/05/29/received PY - 2015/07/29/accepted PY - 2015/8/31/entrez PY - 2015/9/1/pubmed PY - 2017/2/12/medline KW - 3,4-Methylenedioxypyrovalerone (MDPV) KW - Cocaine KW - Methylone KW - Microdialysis KW - Rats KW - Self-administration SP - 1981 EP - 90 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 233 IS - 10 N2 - RATIONALE: 3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called "bath salts" products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT). OBJECTIVES: We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV. METHODS: To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats. RESULTS: MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. In contrast, methylone self-administration (0.3 and 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT. CONCLUSIONS: Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats, suggesting these drugs possess significant abuse liability in humans. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/26319160/Reinforcing_and_neurochemical_effects_of_the_"bath_salts"_constituents_34_methylenedioxypyrovalerone__MDPV__and_34_methylenedioxy_N_methylcathinone__methylone__in_male_rats_ L2 - https://dx.doi.org/10.1007/s00213-015-4057-0 DB - PRIME DP - Unbound Medicine ER -