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Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder.

Wilson CB, McLaughlin LD, Ebenezer PJ, Nair AR, Dange R, Harre JG, Shaak TL, Diamond DM, Francis J - Front Behav Neurosci (2014)

Bottom Line: PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups).At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle.This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting.

View Article: PubMed Central - PubMed

Affiliation: Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University Baton Rouge, LA, USA.

ABSTRACT
Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines (PIC) are elevated during the progression of the disorder. Currently, the only approved pharmacologic treatments for PTSD are the selective-serotonin reuptake inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness. Thus, this study sought to analyze the effects of the SSRI sertraline on inflammation and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. We hypothesized that sertraline would diminish inflammatory components and increase 5-HT but might also affect levels of other neurotransmitters, particularly NE. PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle. The animals were subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and normalized 5-HT levels in the central nervous system (CNS). In contrast, sertraline produced elevations in NE in the CNS and systemic circulation of SSRI treated PTSD and control groups. This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting.

No MeSH data available.


Related in: MedlinePlus

Elevated plus-maze performance: between group measurements. After sertraline treatment, the PTSD + Sert group demonstrated no measureable improvement vs. the control + Sert group, and the PTSD + Veh group displayed persistent anxiety vs. the control + Veh group (A). There were no differences in overall ambulations in any of the four groups after the treatment period (B). All data are presented as mean ± SEM. *p < 0.05 between the treatment groups. #p < 0.05 between the vehicle groups.
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Figure 2: Elevated plus-maze performance: between group measurements. After sertraline treatment, the PTSD + Sert group demonstrated no measureable improvement vs. the control + Sert group, and the PTSD + Veh group displayed persistent anxiety vs. the control + Veh group (A). There were no differences in overall ambulations in any of the four groups after the treatment period (B). All data are presented as mean ± SEM. *p < 0.05 between the treatment groups. #p < 0.05 between the vehicle groups.

Mentions: Prior to the start of the stress regimen, there were no differences noted in baseline open arm exploration (Figure 1A) or total arm entries (Figure 1B). After the 31-day stress regimen, the PTSD group spent considerably less time in the open vs. closed arms as compared to the control group, t(22) = 5.10, p < 0.0001, and as compared to baseline, t(22) = 3.86, p < 0.001 (Figure 1A). Overall ambulations, however, were not affected, F(3,44) = 0.974, p > 0.05 (Figure 1B). After the 7-day sertraline treatment, the PTSD + Sert group displayed no increased open arm exploration vs. the PTSD + Veh group, t(10) = 0.49, p > 0.05, or the control + Sert group, t(10) = 4.59, p < 0.001. The control group also showed no difference between the control + Sert and control + Veh groups, t(10) = 0.43, p > 0.05, (Figure 2A). No differences were found in overall ambulations between or within groups after the sertraline treatment, F(3, 20) = 0.55, p > 0.05 (Figure 2B).


Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder.

Wilson CB, McLaughlin LD, Ebenezer PJ, Nair AR, Dange R, Harre JG, Shaak TL, Diamond DM, Francis J - Front Behav Neurosci (2014)

Elevated plus-maze performance: between group measurements. After sertraline treatment, the PTSD + Sert group demonstrated no measureable improvement vs. the control + Sert group, and the PTSD + Veh group displayed persistent anxiety vs. the control + Veh group (A). There were no differences in overall ambulations in any of the four groups after the treatment period (B). All data are presented as mean ± SEM. *p < 0.05 between the treatment groups. #p < 0.05 between the vehicle groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4115632&req=5

Figure 2: Elevated plus-maze performance: between group measurements. After sertraline treatment, the PTSD + Sert group demonstrated no measureable improvement vs. the control + Sert group, and the PTSD + Veh group displayed persistent anxiety vs. the control + Veh group (A). There were no differences in overall ambulations in any of the four groups after the treatment period (B). All data are presented as mean ± SEM. *p < 0.05 between the treatment groups. #p < 0.05 between the vehicle groups.
Mentions: Prior to the start of the stress regimen, there were no differences noted in baseline open arm exploration (Figure 1A) or total arm entries (Figure 1B). After the 31-day stress regimen, the PTSD group spent considerably less time in the open vs. closed arms as compared to the control group, t(22) = 5.10, p < 0.0001, and as compared to baseline, t(22) = 3.86, p < 0.001 (Figure 1A). Overall ambulations, however, were not affected, F(3,44) = 0.974, p > 0.05 (Figure 1B). After the 7-day sertraline treatment, the PTSD + Sert group displayed no increased open arm exploration vs. the PTSD + Veh group, t(10) = 0.49, p > 0.05, or the control + Sert group, t(10) = 4.59, p < 0.001. The control group also showed no difference between the control + Sert and control + Veh groups, t(10) = 0.43, p > 0.05, (Figure 2A). No differences were found in overall ambulations between or within groups after the sertraline treatment, F(3, 20) = 0.55, p > 0.05 (Figure 2B).

Bottom Line: PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups).At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle.This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting.

View Article: PubMed Central - PubMed

Affiliation: Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University Baton Rouge, LA, USA.

ABSTRACT
Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines (PIC) are elevated during the progression of the disorder. Currently, the only approved pharmacologic treatments for PTSD are the selective-serotonin reuptake inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness. Thus, this study sought to analyze the effects of the SSRI sertraline on inflammation and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. We hypothesized that sertraline would diminish inflammatory components and increase 5-HT but might also affect levels of other neurotransmitters, particularly NE. PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle. The animals were subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and normalized 5-HT levels in the central nervous system (CNS). In contrast, sertraline produced elevations in NE in the CNS and systemic circulation of SSRI treated PTSD and control groups. This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting.

No MeSH data available.


Related in: MedlinePlus