Discriminative-Stimulus Effects of Synthetic Cathinones in Squirrel Monkeys.
Alkaloids
/ administration & dosage
Animals
Behavior, Animal
/ drug effects
Benzodioxoles
/ pharmacology
Central Nervous System Stimulants
/ administration & dosage
Discrimination Learning
/ drug effects
Interoception
/ drug effects
Male
Methamphetamine
/ administration & dosage
N-Methyl-3,4-methylenedioxyamphetamine
/ administration & dosage
Propiophenones
/ pharmacology
Psychotropic Drugs
/ administration & dosage
Pyrrolidines
/ pharmacology
Saimiri
Synthetic Cathinone
MDMA
Methamphetamine
drug-discrimination
monkeys
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
20 08 2021
20 08 2021
Historique:
received:
27
10
2020
revised:
06
04
2021
accepted:
26
04
2021
pubmed:
29
4
2021
medline:
1
2
2022
entrez:
28
4
2021
Statut:
ppublish
Résumé
Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates. The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle. Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects. These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans.
Sections du résumé
BACKGROUND
Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates.
METHODS
The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle.
RESULTS
Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects.
CONCLUSIONS
These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans.
Identifiants
pubmed: 33909067
pii: 6257213
doi: 10.1093/ijnp/pyab017
pmc: PMC8378080
doi:
Substances chimiques
Alkaloids
0
Benzodioxoles
0
Central Nervous System Stimulants
0
Propiophenones
0
Psychotropic Drugs
0
Pyrrolidines
0
alpha-pyrrolidinovalerophenone
0
monomethylpropion
386QA522QG
Methamphetamine
44RAL3456C
cathinone
540EI4406J
mephedrone
8BA8T27317
N-Methyl-3,4-methylenedioxyamphetamine
KE1SEN21RM
methylone
L4I4B1R01F
Synthetic Cathinone
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
656-665Subventions
Organisme : NIDA NIH HHS
ID : R01 DA043700
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM113117
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA048150
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA002519
Pays : United States
Organisme : NIDA NIH HHS
ID : K01 DA039306
Pays : United States
Organisme : NIGMS NIH HHS
ID : R24 GM111385
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.