Tags

Type your tag names separated by a space and hit enter

Evaluation of training dose in male Sprague-Dawley rats trained to discriminate 4-methylmethcathinone.
Psychopharmacology (Berl). 2017 Nov; 234(21):3271-3278.P

Abstract

RATIONALE

Although the synthetic cathinone 4-methylmethcathinone (4-MMC, mephedrone) has been a subject of intensive research investigation, the pharmacological mechanisms involved in its interoceptive stimulus effects have yet to be fully characterized.

OBJECTIVE

The present study employed drug discrimination methods in rats to compare the interoceptive stimulus properties of two different training doses of 4-MMC to other substances with similar pharmacological actions.

METHODS

Sixteen male Sprague-Dawley rats were trained to discriminate either 1.0 mg/kg (N = 8) or 3.0 mg/kg (N = 8) 4-MMC from saline. Substitution tests were conducted with drugs that increase extracellular monoamine levels (d-amphetamine, (+)-methamphetamine, 4-MMC, MDMA, MDPV, and (-)-cocaine), a serotonin releaser (+)-fenfluramine, and a serotonergic (5-HT2A) hallucinogen (+)-LSD.

RESULTS

Stimulus control was established in fewer sessions in the subjects trained with 3.0 mg/kg compared to those trained with 1.0 mg/kg 4-MMC. Cocaine, MDMA, and d-amphetamine produced full substitution in the 1.0 mg/kg 4-MMC-trained rats at doses that did not decrease response rate. However, doses of test drugs that engendered > 80% 4-MMC-lever selection concurrently produced rate-decreasing effects in rats trained to discriminate 3.0 mg/kg 4-MMC.

CONCLUSIONS

These findings further characterize the interoceptive stimulus effects of 4-MMC and indicate that these effects vary little with training dose; however, qualitative differences in substitutability of test drugs were observed between training groups. This study expands existing knowledge regarding the psychopharmacology of 4-MMC and the potential neurochemical substrates contributing to its subjective effects.

Authors+Show Affiliations

Department of Psychology, Western Michigan University, Kalamazoo, MI, 49008, USA.Department of Psychology, Western Michigan University, Kalamazoo, MI, 49008, USA.Department of Psychology, Western Michigan University, Kalamazoo, MI, 49008, USA. lisa.baker@wmich.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28815279

Citation

Berquist, Michael D., et al. "Evaluation of Training Dose in Male Sprague-Dawley Rats Trained to Discriminate 4-methylmethcathinone." Psychopharmacology, vol. 234, no. 21, 2017, pp. 3271-3278.
Berquist MD, Thompson NA, Baker LE. Evaluation of training dose in male Sprague-Dawley rats trained to discriminate 4-methylmethcathinone. Psychopharmacology (Berl). 2017;234(21):3271-3278.
Berquist, M. D., Thompson, N. A., & Baker, L. E. (2017). Evaluation of training dose in male Sprague-Dawley rats trained to discriminate 4-methylmethcathinone. Psychopharmacology, 234(21), 3271-3278. https://doi.org/10.1007/s00213-017-4716-4
Berquist MD, Thompson NA, Baker LE. Evaluation of Training Dose in Male Sprague-Dawley Rats Trained to Discriminate 4-methylmethcathinone. Psychopharmacology (Berl). 2017;234(21):3271-3278. PubMed PMID: 28815279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of training dose in male Sprague-Dawley rats trained to discriminate 4-methylmethcathinone. AU - Berquist,Michael D,2nd AU - Thompson,Nathyn A, AU - Baker,Lisa E, Y1 - 2017/08/16/ PY - 2016/09/25/received PY - 2017/08/03/accepted PY - 2017/8/18/pubmed PY - 2018/5/15/medline PY - 2017/8/18/entrez KW - 4-MMC KW - 4-methylmethcathinone KW - Bath salts KW - Drug discrimination KW - Mephedrone KW - Synthetic cathinone SP - 3271 EP - 3278 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 234 IS - 21 N2 - RATIONALE: Although the synthetic cathinone 4-methylmethcathinone (4-MMC, mephedrone) has been a subject of intensive research investigation, the pharmacological mechanisms involved in its interoceptive stimulus effects have yet to be fully characterized. OBJECTIVE: The present study employed drug discrimination methods in rats to compare the interoceptive stimulus properties of two different training doses of 4-MMC to other substances with similar pharmacological actions. METHODS: Sixteen male Sprague-Dawley rats were trained to discriminate either 1.0 mg/kg (N = 8) or 3.0 mg/kg (N = 8) 4-MMC from saline. Substitution tests were conducted with drugs that increase extracellular monoamine levels (d-amphetamine, (+)-methamphetamine, 4-MMC, MDMA, MDPV, and (-)-cocaine), a serotonin releaser (+)-fenfluramine, and a serotonergic (5-HT2A) hallucinogen (+)-LSD. RESULTS: Stimulus control was established in fewer sessions in the subjects trained with 3.0 mg/kg compared to those trained with 1.0 mg/kg 4-MMC. Cocaine, MDMA, and d-amphetamine produced full substitution in the 1.0 mg/kg 4-MMC-trained rats at doses that did not decrease response rate. However, doses of test drugs that engendered > 80% 4-MMC-lever selection concurrently produced rate-decreasing effects in rats trained to discriminate 3.0 mg/kg 4-MMC. CONCLUSIONS: These findings further characterize the interoceptive stimulus effects of 4-MMC and indicate that these effects vary little with training dose; however, qualitative differences in substitutability of test drugs were observed between training groups. This study expands existing knowledge regarding the psychopharmacology of 4-MMC and the potential neurochemical substrates contributing to its subjective effects. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/28815279/Evaluation_of_training_dose_in_male_Sprague_Dawley_rats_trained_to_discriminate_4_methylmethcathinone_ L2 - https://dx.doi.org/10.1007/s00213-017-4716-4 DB - PRIME DP - Unbound Medicine ER -