New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents.
Animals
Designer Drugs
/ administration & dosage
Dopamine
/ metabolism
Dose-Response Relationship, Drug
Inflammation
/ chemically induced
Locomotion
/ drug effects
Male
Mice
Mice, Inbred C57BL
Neurotoxicity Syndromes
/ etiology
Nucleus Accumbens
/ drug effects
Phenethylamines
/ administration & dosage
Prefrontal Cortex
/ drug effects
Rats
Rats, Sprague-Dawley
2C-C
2C-P
Abuse potential
Neurotoxicity
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
18
08
2020
accepted:
04
01
2021
pubmed:
31
1
2021
medline:
4
11
2021
entrez:
30
1
2021
Statut:
ppublish
Résumé
2C (2C-x) is the general name for the family of phenethylamines containing two methoxy groups at the 2 and 5 positions of the benzene ring. The abuse of 2C family drugs has grown rapidly, although the abuse potential and neurotoxic properties of 2C drugs have not yet been fully investigated. In this study, we investigated the abuse potential and neurotoxicity of 4-chloro-2,5-dimethoxyphenethylamine (2C-C) and 2,5-dimethoxy-4-propylphenethylamine (2C-P). We found that 2C-C and 2C-P produced conditioned place preference in a dose-dependent manner in mice, and increased self-administration in rats, suggesting that 2C-C and 2C-P have abuse potential. To investigate the neurotoxicity of 2C-C and 2C-P, we examined motor performance and memory impairment after high doses of 2C-C and 2C-P. High doses of 2C-C and 2C-P decreased locomotor activity, rota-rod performance, and lower Y-maze test, novel objective recognition test, and passive avoidance test scores. We also observed that 2C-C and 2C-P affected expression levels of the D1 dopamine receptor, D2 dopamine receptor, dopamine transporter, and phospho-dopamine transporter in the nucleus accumbens and the medial prefrontal cortex, and increased c-Fos immuno-positive cells in the nucleus accumbens. Moreover, high doses of 2C-C and 2C-P induced microglial activation, which is involved in the inflammatory reaction in the striatum. These results suggest that 2C-C and 2C-P have abuse potential by affecting dopaminergic signaling and induce neurotoxicity via initiating neuroinflammation at high doses.
Identifiants
pubmed: 33515270
doi: 10.1007/s00204-021-02980-x
pii: 10.1007/s00204-021-02980-x
doi:
Substances chimiques
2,5-dimethoxy-4-n-propylthiophenethylamine
0
Designer Drugs
0
Phenethylamines
0
Dopamine
VTD58H1Z2X
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1413-1429Commentaires et corrections
Type : ErratumIn
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