Sex-dependent effects of early maternal deprivation on MDMA-induced conditioned place preference in adolescent rats: possible neurochemical correlates.
Alvaro Llorente‐berzal, Carmen Manzanedo, Manuel Daza‐losada, Manuel Valero, Meritxell López-Gallardo, María A. Aguilar, Marta Rodríguez‐arias, José Miñarro, María‐paz Viveros
Toxicology September 6, 2013 DOI: 10.1016/j.tox.2012.12.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent Wistar rats of both sexes; neonatally maternally deprived or control |
| Interventions | MDMA maternal deprivation |
| Dose | 2.5 mg/kg MDMA |
| Duration | Conditioning during periadolescence (PND 34-43); open-field test at end of adolescence (PND 60); sacrifice on PND 68-75 |
| Measures | conditioned place preference (CPP), open-field test, serotonin (5-HT), 5-hydroxyindole acetic acid, CB1 cannabinoid receptor (CB1R) expression, corticosterone, leptin |
| Topics | MDMA |
| Keywords | Adolescence Cb1 receptor Conditioned place preference Maternal deprivation Serotonergic system |
| Key findings | Maternal deprivation reduced MDMA-induced conditioned place preference in male but not female adolescent rats, with control males showing preference while control females and deprived males did not. In MDMA-treated deprived males, striatal and cortical serotonin levels were reduced, hippocampal CB1 receptor expression was increased, and circulating leptin showed a marked trend toward higher levels. |
Abstract
The early neonatal stage constitutes a sensitive period during which exposure to adverse events can increase the risk of neuropsychiatric disorders. Maternal deprivation (MD) is a model of early life stress that induces long-term behavioural and physiological alterations, including susceptibility to different drugs of abuse. In the present study we have used the conditioned place preference (CPP) paradigm to address the influence of MD on the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in adolescent animals of both sexes. We have previously observed in adolescent rats that MD induces modifications in the serotonergic and endocannabinoid systems, which play a role in the rewarding effects of MDMA. In light of this evidence, we hypothesized that MD would alter the psychobiological consequences of exposure to MDMA. Neonatal Wistar rats underwent MD (24h, on PND 9) or were left undisturbed (controls). The animals were conditioned with 2.5mg/kg MDMA during the periadolescent period (PND 34-PND 43) and were tested in the open-field test at the end of adolescence (PND 60). Animals were sacrificed on PND 68-75 and levels of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid were measured in the striatum, hippocampus and cortex, while the expression of hippocampal CB1 cannabinoid receptor (CB1R) and circulating levels of corticosterone and leptin were also measured. Control males showed CPP after administration of MDMA. However, no MDMA-induced CPP was detected in control females or MD males, and MD had no effect on open field activity in any group. A reduction in striatal and cortical 5-HT levels, increased expression of hippocampal CB1R and a marked trend towards higher circulating leptin levels were observed in MDMA-treated MD males. Our results demonstrate for the first time that MD reduces the rewarding effects of MDMA in a sex-dependent manner. We propose that this effect is related, at least in part, with alterations of the serotonergic and cannabinoid systems.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice Behavioural Pharmacology September 1, 2014
- Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment. Pharmacological Research December 1, 2021
- A Systematic Review of the MDMA Model to Address Social Impairment in Autism. Current Neuropharmacology 2021
- Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 3, 2014
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