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Abuse-related and abuse-limiting effects of methcathinone and the synthetic "bath salts" cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats.
Psychopharmacology (Berl). 2014 Jan; 231(1):199-207.P

Abstract

RATIONALE

Abuse of synthetic cathinones, popularized as "bath salts," has increased dramatically in the USA since their debut in 2010. Preclinical behavioral studies may clarify determinants of the abuse-related effects produced by these compounds.

OBJECTIVES

This study examined behavioral effects of (±)-methcathinone, (±)-3,4-methylenedioxypyrovalerone (MDPV), (±)-3,4-methylenedioxymethcathinone (methylone), and (±)-4-methylmethcathinone (mephedrone) in rats using intracranial self-stimulation (ICSS).

METHODS

Male Sprague-Dawley rats (n = 18) with electrodes targeting the medial forebrain bundle responded for multiple frequencies of brain stimulation and were tested in two phases. First, dose-effect curves for methcathinone (0.1-1.0 mg/kg), MDPV (0.32-3.2 mg/kg), methylone (1.0-10 mg/kg), and mephedrone (1.0-10 mg/kg) were determined. Second, time courses were determined for effects produced by the highest dose of each compound.

RESULTS

Methcathinone produced dose- and time-dependent facilitation of ICSS. MDPV, methylone, and mephedrone produced dose- and time-dependent increases in low rates of ICSS maintained by low brain stimulation frequencies, but also produced abuse-limiting depression of high ICSS rates maintained by high brain stimulation frequencies. Efficacies to facilitate ICSS were methcathinone ≥ MDPV ≥ methylone > mephedrone. Methcathinone was the most potent compound, and MDPV was the longest acting compound.

CONCLUSIONS

All compounds facilitated ICSS at some doses and pretreatment times, which is consistent with abuse liability for each of these compounds. However, efficacies of compounds to facilitate ICSS varied, with methcathinone displaying the highest efficacy and mephedrone displaying the lowest efficacy to facilitate ICSS.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, PO Box 980613, Richmond, VA, 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23949206

Citation

Bonano, J S., et al. "Abuse-related and Abuse-limiting Effects of Methcathinone and the Synthetic "bath Salts" Cathinone Analogs Methylenedioxypyrovalerone (MDPV), Methylone and Mephedrone On Intracranial Self-stimulation in Rats." Psychopharmacology, vol. 231, no. 1, 2014, pp. 199-207.
Bonano JS, Glennon RA, De Felice LJ, et al. Abuse-related and abuse-limiting effects of methcathinone and the synthetic "bath salts" cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats. Psychopharmacology (Berl). 2014;231(1):199-207.
Bonano, J. S., Glennon, R. A., De Felice, L. J., Banks, M. L., & Negus, S. S. (2014). Abuse-related and abuse-limiting effects of methcathinone and the synthetic "bath salts" cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats. Psychopharmacology, 231(1), 199-207. https://doi.org/10.1007/s00213-013-3223-5
Bonano JS, et al. Abuse-related and Abuse-limiting Effects of Methcathinone and the Synthetic "bath Salts" Cathinone Analogs Methylenedioxypyrovalerone (MDPV), Methylone and Mephedrone On Intracranial Self-stimulation in Rats. Psychopharmacology (Berl). 2014;231(1):199-207. PubMed PMID: 23949206.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Abuse-related and abuse-limiting effects of methcathinone and the synthetic "bath salts" cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats. AU - Bonano,J S, AU - Glennon,R A, AU - De Felice,L J, AU - Banks,M L, AU - Negus,S S, Y1 - 2013/08/15/ PY - 2013/04/01/received PY - 2013/07/20/accepted PY - 2013/8/17/entrez PY - 2013/8/21/pubmed PY - 2014/8/19/medline SP - 199 EP - 207 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 231 IS - 1 N2 - RATIONALE: Abuse of synthetic cathinones, popularized as "bath salts," has increased dramatically in the USA since their debut in 2010. Preclinical behavioral studies may clarify determinants of the abuse-related effects produced by these compounds. OBJECTIVES: This study examined behavioral effects of (±)-methcathinone, (±)-3,4-methylenedioxypyrovalerone (MDPV), (±)-3,4-methylenedioxymethcathinone (methylone), and (±)-4-methylmethcathinone (mephedrone) in rats using intracranial self-stimulation (ICSS). METHODS: Male Sprague-Dawley rats (n = 18) with electrodes targeting the medial forebrain bundle responded for multiple frequencies of brain stimulation and were tested in two phases. First, dose-effect curves for methcathinone (0.1-1.0 mg/kg), MDPV (0.32-3.2 mg/kg), methylone (1.0-10 mg/kg), and mephedrone (1.0-10 mg/kg) were determined. Second, time courses were determined for effects produced by the highest dose of each compound. RESULTS: Methcathinone produced dose- and time-dependent facilitation of ICSS. MDPV, methylone, and mephedrone produced dose- and time-dependent increases in low rates of ICSS maintained by low brain stimulation frequencies, but also produced abuse-limiting depression of high ICSS rates maintained by high brain stimulation frequencies. Efficacies to facilitate ICSS were methcathinone ≥ MDPV ≥ methylone > mephedrone. Methcathinone was the most potent compound, and MDPV was the longest acting compound. CONCLUSIONS: All compounds facilitated ICSS at some doses and pretreatment times, which is consistent with abuse liability for each of these compounds. However, efficacies of compounds to facilitate ICSS varied, with methcathinone displaying the highest efficacy and mephedrone displaying the lowest efficacy to facilitate ICSS. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/23949206/Abuse_related_and_abuse_limiting_effects_of_methcathinone_and_the_synthetic_"bath_salts"_cathinone_analogs_methylenedioxypyrovalerone__MDPV__methylone_and_mephedrone_on_intracranial_self_stimulation_in_rats_ L2 - https://dx.doi.org/10.1007/s00213-013-3223-5 DB - PRIME DP - Unbound Medicine ER -