Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences
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-m...
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| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/10/2336 |
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| author | Augusta Pisanu Giacomo Lo Russo Giuseppe Talani Jessica Bratzu Carlotta Siddi Fabrizio Sanna Marco Diana Patrizia Porcu Maria Antonietta De Luca Liana Fattore |
| author_facet | Augusta Pisanu Giacomo Lo Russo Giuseppe Talani Jessica Bratzu Carlotta Siddi Fabrizio Sanna Marco Diana Patrizia Porcu Maria Antonietta De Luca Liana Fattore |
| author_sort | Augusta Pisanu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:40:23Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:40:23Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ec8fbdd30ece49b2b03a6cd5e1da96bf2023-11-23T23:01:24ZengMDPI AGBiomedicines2227-90592022-09-011010233610.3390/biomedicines10102336Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex DifferencesAugusta Pisanu0Giacomo Lo Russo1Giuseppe Talani2Jessica Bratzu3Carlotta Siddi4Fabrizio Sanna5Marco Diana6Patrizia Porcu7Maria Antonietta De Luca8Liana Fattore9CNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyCNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyCNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyCNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042 Cagliari, Italy‘G. Minardi’ Cognitive Neuroscience Laboratory, Department of Chemical, Physical, Mathematical and Biological Sciences, University of Sassari, Via Vienna 2, 07100 Sassari, ItalyCNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyCNR Institute of Neuroscience-Cagliari, National Research Council-Italy, Cittadella Universitaria, Monserrato, 09042 Cagliari, ItalyThe 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.https://www.mdpi.com/2227-9059/10/10/2336novel psychoactive substances (NPSs)cathinonesphenethylaminesabuse liabilitysex differencesVTA |
| spellingShingle | Augusta Pisanu Giacomo Lo Russo Giuseppe Talani Jessica Bratzu Carlotta Siddi Fabrizio Sanna Marco Diana Patrizia Porcu Maria Antonietta De Luca Liana Fattore Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences Biomedicines novel psychoactive substances (NPSs) cathinones phenethylamines abuse liability sex differences VTA |
| title | Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences |
| title_full | Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences |
| title_fullStr | Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences |
| title_full_unstemmed | Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences |
| title_short | Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences |
| title_sort | effects of the phenethylamine 2 cl 4 5 mdma and the synthetic cathinone 3 4 mdphp in adolescent rats focus on sex differences |
| topic | novel psychoactive substances (NPSs) cathinones phenethylamines abuse liability sex differences VTA |
| url | https://www.mdpi.com/2227-9059/10/10/2336 |
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