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.
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_
DB - PRIME
DP - Unbound Medicine
ER -
