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

Ruda-Kucerova J, Amchova P, Babinska Z, Dusek L, Micale V, Sulcova A - Front Psychiatry (2015)

Bottom Line: Females were found to self-administer significantly lower dose of METH.Females displayed approximately 300% of active nose-pokes compared to 50% in males.This effect was detected in all females, independently of current phase of their estrous cycle.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Reinstatement of methamphetamine seeking behavior in male and female rats. The graphs show a percent of mean basal nose-poking (14 days of acquisition and maintenance) and number of nose-pokes in the reinstatement session in male and female rats. There was a statistically significant difference between the sexes in both measures: male rats showed mean % of responding 48.3% and females 295.7% (mixed ANOVA model, p = 0.001). The apparent difference between the sexes is further confirmed by behavioral activity reflected in a mean number of nose-pokes: 41.0 in males and 136.5 in females (mixed ANOVA model, p = 0.006).
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Figure 3: Reinstatement of methamphetamine seeking behavior in male and female rats. The graphs show a percent of mean basal nose-poking (14 days of acquisition and maintenance) and number of nose-pokes in the reinstatement session in male and female rats. There was a statistically significant difference between the sexes in both measures: male rats showed mean % of responding 48.3% and females 295.7% (mixed ANOVA model, p = 0.001). The apparent difference between the sexes is further confirmed by behavioral activity reflected in a mean number of nose-pokes: 41.0 in males and 136.5 in females (mixed ANOVA model, p = 0.006).

Mentions: After the 2-week-long period of forced abstinence one last reinstatement session was performed with no drug availability. The only measure of the drug-seeking behavior is the number of active operandum responses. This number was converted to a percent of mean basal nose-poking (14 days of acquisition and maintenance). There was a massive difference between the sexes recorded: male rats showed mean percent of responding 48.3% whereas females showed 295.7% (mixed ANOVA model, p = 0.001). Results are reported on the Figure 3.


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

Ruda-Kucerova J, Amchova P, Babinska Z, Dusek L, Micale V, Sulcova A - Front Psychiatry (2015)

Reinstatement of methamphetamine seeking behavior in male and female rats. The graphs show a percent of mean basal nose-poking (14 days of acquisition and maintenance) and number of nose-pokes in the reinstatement session in male and female rats. There was a statistically significant difference between the sexes in both measures: male rats showed mean % of responding 48.3% and females 295.7% (mixed ANOVA model, p = 0.001). The apparent difference between the sexes is further confirmed by behavioral activity reflected in a mean number of nose-pokes: 41.0 in males and 136.5 in females (mixed ANOVA model, p = 0.006).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492081&req=5

Figure 3: Reinstatement of methamphetamine seeking behavior in male and female rats. The graphs show a percent of mean basal nose-poking (14 days of acquisition and maintenance) and number of nose-pokes in the reinstatement session in male and female rats. There was a statistically significant difference between the sexes in both measures: male rats showed mean % of responding 48.3% and females 295.7% (mixed ANOVA model, p = 0.001). The apparent difference between the sexes is further confirmed by behavioral activity reflected in a mean number of nose-pokes: 41.0 in males and 136.5 in females (mixed ANOVA model, p = 0.006).
Mentions: After the 2-week-long period of forced abstinence one last reinstatement session was performed with no drug availability. The only measure of the drug-seeking behavior is the number of active operandum responses. This number was converted to a percent of mean basal nose-poking (14 days of acquisition and maintenance). There was a massive difference between the sexes recorded: male rats showed mean percent of responding 48.3% whereas females showed 295.7% (mixed ANOVA model, p = 0.001). Results are reported on the Figure 3.

Bottom Line: Females were found to self-administer significantly lower dose of METH.Females displayed approximately 300% of active nose-pokes compared to 50% in males.This effect was detected in all females, independently of current phase of their estrous cycle.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus