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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

CSF and plasma NE levels. In the CSF, NE was elevated in the PTSD + Veh vs. the control + Veh group and in the control + Sert vs. the control + Veh group. NE was further elevated in the PTSD + Sert vs. the PTSD + Veh group (A). In the plasma, NE was higher in the treatment groups, but it did not reach significance in any comparisons (B). All data are presented as mean ± SEM. *p < 0.05 between the PTSD groups. @p < 0.05 between the control groups. #p < 0.05 between the vehicle groups.
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Figure 3: CSF and plasma NE levels. In the CSF, NE was elevated in the PTSD + Veh vs. the control + Veh group and in the control + Sert vs. the control + Veh group. NE was further elevated in the PTSD + Sert vs. the PTSD + Veh group (A). In the plasma, NE was higher in the treatment groups, but it did not reach significance in any comparisons (B). All data are presented as mean ± SEM. *p < 0.05 between the PTSD groups. @p < 0.05 between the control groups. #p < 0.05 between the vehicle groups.

Mentions: In the CSF, NE was elevated in the PTSD + Veh vs. the control + Veh group, t(8) = 4.22, p < 0.01. Sertraline raised NE levels in the control + Sert vs. the control + Veh group, t(8) = 4.96, p < 0.02, and NE was further elevated in the PTSD + Sert vs. the PTSD + Veh group, t(8) = 3.72, p < 0.01 (Figure 3A). In the plasma, NE was higher in the treatment groups, but it did not reach significance in any comparisons (Figure 3B).


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)

CSF and plasma NE levels. In the CSF, NE was elevated in the PTSD + Veh vs. the control + Veh group and in the control + Sert vs. the control + Veh group. NE was further elevated in the PTSD + Sert vs. the PTSD + Veh group (A). In the plasma, NE was higher in the treatment groups, but it did not reach significance in any comparisons (B). All data are presented as mean ± SEM. *p < 0.05 between the PTSD groups. @p < 0.05 between the control 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 3: CSF and plasma NE levels. In the CSF, NE was elevated in the PTSD + Veh vs. the control + Veh group and in the control + Sert vs. the control + Veh group. NE was further elevated in the PTSD + Sert vs. the PTSD + Veh group (A). In the plasma, NE was higher in the treatment groups, but it did not reach significance in any comparisons (B). All data are presented as mean ± SEM. *p < 0.05 between the PTSD groups. @p < 0.05 between the control groups. #p < 0.05 between the vehicle groups.
Mentions: In the CSF, NE was elevated in the PTSD + Veh vs. the control + Veh group, t(8) = 4.22, p < 0.01. Sertraline raised NE levels in the control + Sert vs. the control + Veh group, t(8) = 4.96, p < 0.02, and NE was further elevated in the PTSD + Sert vs. the PTSD + Veh group, t(8) = 3.72, p < 0.01 (Figure 3A). In the plasma, NE was higher in the treatment groups, but it did not reach significance in any comparisons (Figure 3B).

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