Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats

Preventing relapse to drug abuse is one of the struggles faced by clinicians in order to treat patients with substance use disorders (DSM-5). There is a large body of clinical evidence suggesting differential characteristics of the disorder in men and women, which is in line with preclinical finding...

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Main Authors: Ruda-Kucerova, Jana, Amchova, Petra, Babinska, Zuzana, Dusek, Ladislav, Micale, Vincenzo, Sulcova, Alexandra
Format: Online
Language:English
Published: Frontiers Media S.A. 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492081/
id pubmed-4492081
recordtype oai_dc
spelling pubmed-44920812015-07-27 Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats Ruda-Kucerova, Jana Amchova, Petra Babinska, Zuzana Dusek, Ladislav Micale, Vincenzo Sulcova, Alexandra Psychiatry Preventing relapse to drug abuse is one of the struggles faced by clinicians in order to treat patients with substance use disorders (DSM-5). There is a large body of clinical evidence suggesting differential characteristics of the disorder in men and women, which is in line with preclinical findings as well. The aim of this study was to assess differences in relapse-like behavior in methamphetamine (METH) seeking after a period of forced abstinence, which simulates the real clinical situation very well. Findings from such study might add new insights in gender differences in relapse mechanisms to previous studies, which employ a classical drug or cue-induced reinstatement procedure following the extinction training. Adult male and female Sprague-Dawley rats were used in IV self-administration procedure conducted in operant boxes using nose-poke operandi (Coulborn Instruments, USA). Active nose-poke resulted in activation of the infusion pump to deliver one intravenous infusion of METH (0.08 mg/kg). After baseline drug intake was established (maintenance phase), a period of forced abstinence was initiated and rats were kept singly in their home cages for 14 days. Finally, one reinstatement session in operant boxes was conducted. Females were found to self-administer significantly lower dose of METH. The relapse rate was assessed as a number of active nose-pokes during the reinstatement session, expressed as a percentage of active nose-poking during the maintenance phase. Females displayed approximately 300% of active nose-pokes compared to 50% in males. This indicates higher vulnerability to relapse of METH seeking behavior in female rats. This effect was detected in all females, independently of current phase of their estrous cycle. Therefore, this paradigm using operant drug self-administration and reinstatement of drug-seeking after forced abstinence model can be used for preclinical screening for potential new anti-relapse medications specific for women. Frontiers Media S.A. 2015-07-06 /pmc/articles/PMC4492081/ /pubmed/26217239 http://dx.doi.org/10.3389/fpsyt.2015.00091 Text en Copyright © 2015 Ruda-Kucerova, Amchova, Babinska, Dusek, Micale and Sulcova. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ruda-Kucerova, Jana
Amchova, Petra
Babinska, Zuzana
Dusek, Ladislav
Micale, Vincenzo
Sulcova, Alexandra
spellingShingle Ruda-Kucerova, Jana
Amchova, Petra
Babinska, Zuzana
Dusek, Ladislav
Micale, Vincenzo
Sulcova, Alexandra
Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats
author_facet Ruda-Kucerova, Jana
Amchova, Petra
Babinska, Zuzana
Dusek, Ladislav
Micale, Vincenzo
Sulcova, Alexandra
author_sort Ruda-Kucerova, Jana
title Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats
title_short Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats
title_full Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats
title_fullStr Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats
title_full_unstemmed Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats
title_sort sex differences in the reinstatement of methamphetamine seeking after forced abstinence in sprague-dawley rats
description Preventing relapse to drug abuse is one of the struggles faced by clinicians in order to treat patients with substance use disorders (DSM-5). There is a large body of clinical evidence suggesting differential characteristics of the disorder in men and women, which is in line with preclinical findings as well. The aim of this study was to assess differences in relapse-like behavior in methamphetamine (METH) seeking after a period of forced abstinence, which simulates the real clinical situation very well. Findings from such study might add new insights in gender differences in relapse mechanisms to previous studies, which employ a classical drug or cue-induced reinstatement procedure following the extinction training. Adult male and female Sprague-Dawley rats were used in IV self-administration procedure conducted in operant boxes using nose-poke operandi (Coulborn Instruments, USA). Active nose-poke resulted in activation of the infusion pump to deliver one intravenous infusion of METH (0.08 mg/kg). After baseline drug intake was established (maintenance phase), a period of forced abstinence was initiated and rats were kept singly in their home cages for 14 days. Finally, one reinstatement session in operant boxes was conducted. Females were found to self-administer significantly lower dose of METH. The relapse rate was assessed as a number of active nose-pokes during the reinstatement session, expressed as a percentage of active nose-poking during the maintenance phase. Females displayed approximately 300% of active nose-pokes compared to 50% in males. This indicates higher vulnerability to relapse of METH seeking behavior in female rats. This effect was detected in all females, independently of current phase of their estrous cycle. Therefore, this paradigm using operant drug self-administration and reinstatement of drug-seeking after forced abstinence model can be used for preclinical screening for potential new anti-relapse medications specific for women.
publisher Frontiers Media S.A.
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492081/
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