title: Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced Abstinence in Sprague-Dawley Rats.
abstract: 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.
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, Central European Institute of Technology (CEITEC), Masaryk University , Brno , Czech Republic ; Department of Pharmacology, Faculty of Medicine, Masaryk University , Brno , Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Ruda-Kucerova
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, Central European Institute of Technology (CEITEC), Masaryk University , Brno , Czech Republic ; Department of Pharmacology, Faculty of Medicine, Masaryk University , Brno , Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Amchova
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, Central European Institute of Technology (CEITEC), Masaryk University , Brno , Czech Republic ; Department of Pharmacology, Faculty of Medicine, Masaryk University , Brno , Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Babinska
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University , Brno , Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Dusek
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, Central European Institute of Technology (CEITEC), Masaryk University , Brno , Czech Republic ; Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania , Catania , Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Micale
authors.affiliation: Experimental and Applied Neuropsychopharmacology Group, Central European Institute of Technology (CEITEC), Masaryk University , Brno , Czech Republic.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sulcova
keywords: Sprague-Dawley rats; forced abstinence; methamphetamine; reinstatement of drug-seeking behavior; sex/gender differences