Effects of the Phenethylamine 2-Cl-4,5-MDMA and the Synthetic Cathinone 3,4-MDPHP in Adolescent Rats: Focus on Sex Differences.
Augusta Pisanu, Giacomo Lo Russo, Giuseppe Talani, Jessica Bratzu, Carlotta Siddi, Fabrizio Sanna, Marco Diana, Patrizia Porcu, Maria Antonietta De Luca, Liana Fattore
Biomedicines September 20, 2022 DOI: 10.3390/biomedicines10102336 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male and female adolescent rats |
| Interventions | 2-chloro-4 5-methylenedioxymethamphetamine (2-Cl-4 5-MDMA) 3 4-methylenedioxy-α-pyrrolidinohexanophenone (3 4-MDPHP) |
| Topics | MDMA |
| Keywords | Vta Abuse liability Cathinones Corticosterone Dopamine Phenethylamines Sex differences |
| Key findings | Neither 2-Cl-4,5-MDMA nor 3,4-MDPHP sustained reliable self-administration in rats, with cumulative drug injections not significantly different from saline. Females but not males showed higher plasma corticosterone after chronic low-level 3,4-MDPHP, and both drugs increased rVTA dopaminergic neuron firing in males but not females. The authors conclude these NPSs are unlikely to induce dependence in occasional users but may cause sex-dimorphic central and peripheral effects. |
Abstract
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.