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 -