Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences.

Autor: Pisanu A; CNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., Lo Russo G; CNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., Talani G; CNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., Bratzu J; CNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., Siddi C; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., Sanna F; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., Diana M; 'G. Minardi' Cognitive Neuroscience Laboratory, Department of Chemical, Physical, Mathematical and Biological Sciences, University of Sassari, Via Vienna 2, 07100 Sassari, Italy., Porcu P; CNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., De Luca MA; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy., Fattore L; CNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy.
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2022 Sep 20; Vol. 10 (10). Date of Electronic Publication: 2022 Sep 20.
DOI: 10.3390/biomedicines10102336
Abstrakt: The illicit drug market of novel psychoactive substances (NPSs) is expanding, becoming an alarming threat due to increasing intoxication cases and insufficient (if any) knowledge of their effects. Phenethylamine 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) and synthetic cathinone 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) are new, emerging NPSs suggested to be particularly dangerous. This study verified whether these two new drugs (i) possess abuse liability, (ii) alter plasma corticosterone levels, and (iii) interfere with dopaminergic transmission; male and female adolescent rats were included to evaluate potential sex differences in the drug-induced effects. Findings show that the two NPSs are not able to sustain reliable self-administration behavior in rats, with cumulatively earned injections of drugs being not significantly different from cumulatively earned injections of saline in control groups. Yet, at the end of the self-administration training, females (but not males) exhibited higher plasma corticosterone levels after chronic exposure to low levels of 3,4-MDPHP (but not of 2-Cl-4,5-MDMA). Finally, electrophysiological patch-clamp recordings in the rostral ventral tegmental area (rVTA) showed that both drugs are able to increase the firing rate of rVTA dopaminergic neurons in males but not in females, confirming the sex dimorphic effects of these two NPSs. Altogether, this study demonstrates that 3,4-MDPHP and 2-Cl-4,5-MDMA are unlikely to induce dependence in occasional users but can induce other effects at both central and peripheral levels that may significantly differ between males and females.
Databáze: MEDLINE