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Effects of dopaminergic and serotonergic compounds in rats trained to discriminate a high and a low training dose of the synthetic cathinone mephedrone.
Psychopharmacology (Berl). 2019 Mar; 236(3):1015-1029.P

Abstract

RATIONALE

The underlying pharmacological mechanisms of mephedrone, especially as related to interactions with different neurotransmitter systems, are a critical area of study as mephedrone continues to be abused.

OBJECTIVE

Direct-acting 5-HT2A/2C receptor agonists and antagonists and D1-3 receptor antagonists were examined in two groups of rats trained to discriminate mephedrone. A high dose of mephedrone was trained to extend previous results with traditional monoamine transporter inhibitors and substrate releasers. A very low dose of mephedrone was trained to preferentially capture serotonergic activity and to minimize the influence of rate-decreasing effects on substitution patterns. Selective 5-HT2A/2C and D1-3 receptor antagonists were examined in both groups.

METHODS

Male Sprague-Dawley rats were trained to discriminate either a low dose of 0.5 mg/kg mephedrone (N = 24) or a high dose of 3.2 mg/kg mephedrone (N = 11) from saline.

RESULTS

In the low training-dose group, mephedrone, MDMA, methamphetamine, d-amphetamine, cocaine, and enantiomers of mephedrone substituted for mephedrone; mCPP partially substituted overall for mephedrone; and DOI, WAY163909, and morphine failed to substitute for mephedrone. In the high training-dose group, only mephedrone and MDMA substituted for mephedrone. Sulpiride produced a small antagonism of the low training dose of mephedrone while SCH23390, SB242084, and ketanserin altered response rates.

CONCLUSIONS

A lower training dose of mephedrone produces a discriminative stimulus fully mimicked by MDMA, methamphetamine, cocaine, and d-amphetamine, whereas a higher training dose of mephedrone requires a discriminative stimulus that was only mimicked by MDMA. Dopaminergic or serotoninergic antagonists failed to produce significant blockade of mephedrone at either training dose.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA, 19140, USA.Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA, 19140, USA.Fox Chase Chemical Diversity Center, Inc., Doylestown, PA, USA.Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, PA, 19140, USA. ellen.walker@temple.edu. Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. ellen.walker@temple.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30980094

Citation

Saber, Iman, et al. "Effects of Dopaminergic and Serotonergic Compounds in Rats Trained to Discriminate a High and a Low Training Dose of the Synthetic Cathinone Mephedrone." Psychopharmacology, vol. 236, no. 3, 2019, pp. 1015-1029.
Saber I, Milewski A, Reitz AB, et al. Effects of dopaminergic and serotonergic compounds in rats trained to discriminate a high and a low training dose of the synthetic cathinone mephedrone. Psychopharmacology (Berl). 2019;236(3):1015-1029.
Saber, I., Milewski, A., Reitz, A. B., Rawls, S. M., & Walker, E. A. (2019). Effects of dopaminergic and serotonergic compounds in rats trained to discriminate a high and a low training dose of the synthetic cathinone mephedrone. Psychopharmacology, 236(3), 1015-1029. https://doi.org/10.1007/s00213-019-05241-z
Saber I, et al. Effects of Dopaminergic and Serotonergic Compounds in Rats Trained to Discriminate a High and a Low Training Dose of the Synthetic Cathinone Mephedrone. Psychopharmacology (Berl). 2019;236(3):1015-1029. PubMed PMID: 30980094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of dopaminergic and serotonergic compounds in rats trained to discriminate a high and a low training dose of the synthetic cathinone mephedrone. AU - Saber,Iman, AU - Milewski,Andrew, AU - Reitz,Allen B, AU - Rawls,Scott M, AU - Walker,Ellen A, Y1 - 2019/04/13/ PY - 2018/05/11/received PY - 2019/03/24/accepted PY - 2020/04/13/pmc-release PY - 2019/4/14/pubmed PY - 2019/8/28/medline PY - 2019/4/14/entrez KW - Drug discrimination KW - Ketanserin KW - MDMA KW - Mephedrone KW - Methamphetamine KW - Psychostimulants KW - Rats KW - SB242084 KW - SCH23390 KW - Sulpiride SP - 1015 EP - 1029 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 236 IS - 3 N2 - RATIONALE: The underlying pharmacological mechanisms of mephedrone, especially as related to interactions with different neurotransmitter systems, are a critical area of study as mephedrone continues to be abused. OBJECTIVE: Direct-acting 5-HT2A/2C receptor agonists and antagonists and D1-3 receptor antagonists were examined in two groups of rats trained to discriminate mephedrone. A high dose of mephedrone was trained to extend previous results with traditional monoamine transporter inhibitors and substrate releasers. A very low dose of mephedrone was trained to preferentially capture serotonergic activity and to minimize the influence of rate-decreasing effects on substitution patterns. Selective 5-HT2A/2C and D1-3 receptor antagonists were examined in both groups. METHODS: Male Sprague-Dawley rats were trained to discriminate either a low dose of 0.5 mg/kg mephedrone (N = 24) or a high dose of 3.2 mg/kg mephedrone (N = 11) from saline. RESULTS: In the low training-dose group, mephedrone, MDMA, methamphetamine, d-amphetamine, cocaine, and enantiomers of mephedrone substituted for mephedrone; mCPP partially substituted overall for mephedrone; and DOI, WAY163909, and morphine failed to substitute for mephedrone. In the high training-dose group, only mephedrone and MDMA substituted for mephedrone. Sulpiride produced a small antagonism of the low training dose of mephedrone while SCH23390, SB242084, and ketanserin altered response rates. CONCLUSIONS: A lower training dose of mephedrone produces a discriminative stimulus fully mimicked by MDMA, methamphetamine, cocaine, and d-amphetamine, whereas a higher training dose of mephedrone requires a discriminative stimulus that was only mimicked by MDMA. Dopaminergic or serotoninergic antagonists failed to produce significant blockade of mephedrone at either training dose. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/30980094/Effects_of_dopaminergic_and_serotonergic_compounds_in_rats_trained_to_discriminate_a_high_and_a_low_training_dose_of_the_synthetic_cathinone_mephedrone_ L2 - https://dx.doi.org/10.1007/s00213-019-05241-z DB - PRIME DP - Unbound Medicine ER -