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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

Acquisition of food self-administration behavior in male and female rats. The (A) part shows the course of the active nose poke preference development during acquisition and maintenance of the food self-administration. The bar graph (B) depicts the mean day the animals reached and kept 70% preference of the active operandum: 4.7 in males and 2.2 in females (Mann–Whitney U test, p = 0.014).
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Figure 4: Acquisition of food self-administration behavior in male and female rats. The (A) part shows the course of the active nose poke preference development during acquisition and maintenance of the food self-administration. The bar graph (B) depicts the mean day the animals reached and kept 70% preference of the active operandum: 4.7 in males and 2.2 in females (Mann–Whitney U test, p = 0.014).

Mentions: The acquisition of food taking behavior (sweet pellets) was assessed in terms of day when the animals started to prefer the active nose-poke more than 70%. Figure 4A shows the development of active nose poke preference (%) over all sessions in male and female rats. Figure 4B reports the mean day for reaching 70% preference of the active operandum, which was 4.7 in males and 2.2 in females (Mann–Whitney U test, p = 0.014). The maintenance phase of the food self-administration was evaluated as a mean number of self-administered pellets during the last 5 days when the intake was stable. Figure 5 depicts the significantly higher pellet intake in female rats as compared to males (138–175 and 51–73, respectively, p ≤ 0.05).


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)

Acquisition of food self-administration behavior in male and female rats. The (A) part shows the course of the active nose poke preference development during acquisition and maintenance of the food self-administration. The bar graph (B) depicts the mean day the animals reached and kept 70% preference of the active operandum: 4.7 in males and 2.2 in females (Mann–Whitney U test, p = 0.014).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Acquisition of food self-administration behavior in male and female rats. The (A) part shows the course of the active nose poke preference development during acquisition and maintenance of the food self-administration. The bar graph (B) depicts the mean day the animals reached and kept 70% preference of the active operandum: 4.7 in males and 2.2 in females (Mann–Whitney U test, p = 0.014).
Mentions: The acquisition of food taking behavior (sweet pellets) was assessed in terms of day when the animals started to prefer the active nose-poke more than 70%. Figure 4A shows the development of active nose poke preference (%) over all sessions in male and female rats. Figure 4B reports the mean day for reaching 70% preference of the active operandum, which was 4.7 in males and 2.2 in females (Mann–Whitney U test, p = 0.014). The maintenance phase of the food self-administration was evaluated as a mean number of self-administered pellets during the last 5 days when the intake was stable. Figure 5 depicts the significantly higher pellet intake in female rats as compared to males (138–175 and 51–73, respectively, p ≤ 0.05).

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