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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 and maintenance of methamphetamine intake in male and female rats. The (A) part shows number of infusions expressed as daily means over the 14 days of acquisition and maintenance of the METH IV self-administration. The bar graph depicts the mean number of infusions over the whole 14 days period. There were no statistically significant differences in this measure (mixed ANOVA model). The (B) part shows in an analogical way the mean dose in milligram per kilogram of METH self-administered by male (n = 6) and female (n = 6) rats. The groups start to differ significantly from the day 10 with t-test results: day 10 (p = 0.021), day 11 (p = 0.049), and day 14 (p = 0.048). The bar graph shows the mean number of infusions over the last 5 days of the maintenance period (day 10–14) when the drug intake started to be significantly higher in male rats (p = 0.038, mixed ANOVA model).
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Figure 2: Acquisition and maintenance of methamphetamine intake in male and female rats. The (A) part shows number of infusions expressed as daily means over the 14 days of acquisition and maintenance of the METH IV self-administration. The bar graph depicts the mean number of infusions over the whole 14 days period. There were no statistically significant differences in this measure (mixed ANOVA model). The (B) part shows in an analogical way the mean dose in milligram per kilogram of METH self-administered by male (n = 6) and female (n = 6) rats. The groups start to differ significantly from the day 10 with t-test results: day 10 (p = 0.021), day 11 (p = 0.049), and day 14 (p = 0.048). The bar graph shows the mean number of infusions over the last 5 days of the maintenance period (day 10–14) when the drug intake started to be significantly higher in male rats (p = 0.038, mixed ANOVA model).

Mentions: The acquisition and maintenance of METH taking behavior were assessed, first, in terms of mean number of infusions self-administered per session and, second, by the mean METH dose per session in milligram per kilogram. Figure 2A shows number of infusions obtained per daily session and mean number of infusions during the entire acquisition phase in male and female rats during the acquisition phase of METH self-administration training. ANOVA revealed no significant effects over the whole period. However, when the number of infusions was converted to a METH dose per kilogram of body weight, males were found to self-administer higher dose at the end of the acquisition phase as compared to females. More specifically, as depicted in the Figure 2B, mean METH intake during the last 5 days of training was significantly higher in males than in females, i.e., 2.5 and 1.5 mg/kg, respectively (mixed ANOVA model: p = 0.038).


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 and maintenance of methamphetamine intake in male and female rats. The (A) part shows number of infusions expressed as daily means over the 14 days of acquisition and maintenance of the METH IV self-administration. The bar graph depicts the mean number of infusions over the whole 14 days period. There were no statistically significant differences in this measure (mixed ANOVA model). The (B) part shows in an analogical way the mean dose in milligram per kilogram of METH self-administered by male (n = 6) and female (n = 6) rats. The groups start to differ significantly from the day 10 with t-test results: day 10 (p = 0.021), day 11 (p = 0.049), and day 14 (p = 0.048). The bar graph shows the mean number of infusions over the last 5 days of the maintenance period (day 10–14) when the drug intake started to be significantly higher in male rats (p = 0.038, mixed ANOVA model).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Acquisition and maintenance of methamphetamine intake in male and female rats. The (A) part shows number of infusions expressed as daily means over the 14 days of acquisition and maintenance of the METH IV self-administration. The bar graph depicts the mean number of infusions over the whole 14 days period. There were no statistically significant differences in this measure (mixed ANOVA model). The (B) part shows in an analogical way the mean dose in milligram per kilogram of METH self-administered by male (n = 6) and female (n = 6) rats. The groups start to differ significantly from the day 10 with t-test results: day 10 (p = 0.021), day 11 (p = 0.049), and day 14 (p = 0.048). The bar graph shows the mean number of infusions over the last 5 days of the maintenance period (day 10–14) when the drug intake started to be significantly higher in male rats (p = 0.038, mixed ANOVA model).
Mentions: The acquisition and maintenance of METH taking behavior were assessed, first, in terms of mean number of infusions self-administered per session and, second, by the mean METH dose per session in milligram per kilogram. Figure 2A shows number of infusions obtained per daily session and mean number of infusions during the entire acquisition phase in male and female rats during the acquisition phase of METH self-administration training. ANOVA revealed no significant effects over the whole period. However, when the number of infusions was converted to a METH dose per kilogram of body weight, males were found to self-administer higher dose at the end of the acquisition phase as compared to females. More specifically, as depicted in the Figure 2B, mean METH intake during the last 5 days of training was significantly higher in males than in females, i.e., 2.5 and 1.5 mg/kg, respectively (mixed ANOVA model: p = 0.038).

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