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Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats.
Drug Alcohol Depend. 2019 06 01; 199:50-58.DA

Abstract

BACKGROUND

The development of novel synthetic psychoactive substances continues to accelerate. There are little or no data on the pharmacological mechanisms, behavioral effects, or abuse liability of many of the newer compounds, despite increasing reports of severe adverse effects in recreational users.

METHODS

The current study investigated the discriminative stimulus and locomotor stimulant effects of a group of synthetic cathinone analogs: N-ethylpentylone, dimethylone, dibutylone, clephedrone, 3',4'-tetramethylene-α-pyrrolidinovalerophenone (TH-PVP). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine, methamphetamine or MDMA from vehicle.

RESULTS

N-Ethylpentylone, dimethylone, dibutylone and clephedrone increased locomotor activity. Maximal effects were similar among the test compounds. Relative potencies were: methamphetamine > N-ethylpentylone > clephedrone > dimethylone > MDMA > cocaine > dibutylone. TH-PVP dose-dependently depressed locomotor activity. N-Ethylpentylone, dimethylone, dibutylone and clephedrone substituted fully for the discriminative stimulus effects of methamphetamine. N-Ethylpentylone, dibutylone and clephedrone fully substituted for cocaine, whereas dimethylone produced a maximum of 67% drug-appropriate responding. Dimethylone, dibutylone and clephedrone fully substituted for MDMA, whereas N-ethylpentylone produced only 50% drug-appropriate responding. TH-PVP produced a maximum of 38% methamphetamine-appropriate responding, 50% cocaine-appropriate responding, and less than 1% MDMA-appropriate responding.

CONCLUSIONS

These data provide initial evidence that the novel psychoactive substances N-ethylpentylone, dimethylone, dibutylone, and clephedrone demonstrate potential for abuse as psychostimulants and/or club drugs, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of methamphetamine, cocaine and/or MDMA. TH-PVP has minimal activity in the assays tested and may have little or no abuse liability.

Authors+Show Affiliations

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107-2699, USA. Electronic address: michael.gatch@unthsc.edu.Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107-2699, USA.Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107-2699, USA.

Pub Type(s)

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

Language

eng

PubMed ID

30986635

Citation

Gatch, Michael B., et al. "Locomotor Activity and Discriminative Stimulus Effects of Five Novel Synthetic Cathinone Analogs in Mice and Rats." Drug and Alcohol Dependence, vol. 199, 2019, pp. 50-58.
Gatch MB, Dolan SB, Forster MJ. Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats. Drug Alcohol Depend. 2019;199:50-58.
Gatch, M. B., Dolan, S. B., & Forster, M. J. (2019). Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats. Drug and Alcohol Dependence, 199, 50-58. https://doi.org/10.1016/j.drugalcdep.2019.02.016
Gatch MB, Dolan SB, Forster MJ. Locomotor Activity and Discriminative Stimulus Effects of Five Novel Synthetic Cathinone Analogs in Mice and Rats. Drug Alcohol Depend. 2019 06 1;199:50-58. PubMed PMID: 30986635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats. AU - Gatch,Michael B, AU - Dolan,Sean B, AU - Forster,Michael J, Y1 - 2019/04/06/ PY - 2018/11/16/received PY - 2019/02/07/revised PY - 2019/02/07/accepted PY - 2020/06/01/pmc-release PY - 2019/4/16/pubmed PY - 2019/12/25/medline PY - 2019/4/16/entrez KW - Abuse liability KW - Cathinones KW - Drug discrimination KW - Entactogens KW - Psychostimulants SP - 50 EP - 58 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 199 N2 - BACKGROUND: The development of novel synthetic psychoactive substances continues to accelerate. There are little or no data on the pharmacological mechanisms, behavioral effects, or abuse liability of many of the newer compounds, despite increasing reports of severe adverse effects in recreational users. METHODS: The current study investigated the discriminative stimulus and locomotor stimulant effects of a group of synthetic cathinone analogs: N-ethylpentylone, dimethylone, dibutylone, clephedrone, 3',4'-tetramethylene-α-pyrrolidinovalerophenone (TH-PVP). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine, methamphetamine or MDMA from vehicle. RESULTS: N-Ethylpentylone, dimethylone, dibutylone and clephedrone increased locomotor activity. Maximal effects were similar among the test compounds. Relative potencies were: methamphetamine > N-ethylpentylone > clephedrone > dimethylone > MDMA > cocaine > dibutylone. TH-PVP dose-dependently depressed locomotor activity. N-Ethylpentylone, dimethylone, dibutylone and clephedrone substituted fully for the discriminative stimulus effects of methamphetamine. N-Ethylpentylone, dibutylone and clephedrone fully substituted for cocaine, whereas dimethylone produced a maximum of 67% drug-appropriate responding. Dimethylone, dibutylone and clephedrone fully substituted for MDMA, whereas N-ethylpentylone produced only 50% drug-appropriate responding. TH-PVP produced a maximum of 38% methamphetamine-appropriate responding, 50% cocaine-appropriate responding, and less than 1% MDMA-appropriate responding. CONCLUSIONS: These data provide initial evidence that the novel psychoactive substances N-ethylpentylone, dimethylone, dibutylone, and clephedrone demonstrate potential for abuse as psychostimulants and/or club drugs, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of methamphetamine, cocaine and/or MDMA. TH-PVP has minimal activity in the assays tested and may have little or no abuse liability. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/30986635/Locomotor_activity_and_discriminative_stimulus_effects_of_five_novel_synthetic_cathinone_analogs_in_mice_and_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(19)30096-1 DB - PRIME DP - Unbound Medicine ER -