Amygdala deep brain stimulation is superior to paroxetine treatment in a rat model of posttraumatic stress disorder

Brain Stimul. 2013 Nov;6(6):837-44. doi: 10.1016/j.brs.2013.05.008. Epub 2013 Jun 25.

Abstract

Background: Posttraumatic stress disorder (PTSD) is a very debilitating disease refractory to current treatment with selective serotonin reuptake inhibitors (SSRIs) in up to 30 percent of patients, illustrating the need for new treatments of PTSD. Neuroimaging studies have shown increased activity of the amygdala of patients with PTSD.

Objective/hypothesis: To investigate amygdala deep brain stimulation (DBS) as a possible novel treatment for PTSD and compare it to current treatment with a commonly used SSRI, paroxetine, in a rat PTSD model.

Methods: A PTSD model was created by subjecting rats to inescapable foot shocks in the presence of a conspicuous ball. Response to treatment was measured as a decreased burying behavior when presented with the same ball 1 and 2 weeks after the shocks. Rats were treated with either daily intraperitoneal paroxetine injections or amygdala DBS via an electrode implanted 1 week prior to shocks. Generalized anxiety was assessed using an elevated plus maze.

Results: Animals treated with amygdala DBS showed less ball burying at 2 weeks relative to the animals treated with paroxetine. The animals treated with paroxetine, however, had a lower general anxiety level compared to the DBS-treated group.

Conclusions: In this PTSD model, paroxetine was found to decrease the measured general anxiety level of rats that underwent the PTSD protocol, but did not counteract shock-induced hyper-vigilance toward the trauma-associated object (ball). Amygdala DBS, however, did decrease shock-induced hyper-vigilance as measured by a lower burying time, but had no effect on general anxiety assessed in the elevated plus maze. By attenuating amygdala function, DBS may act to treat the cause of PTSD, hyperactive amygdala function, and may be a promising novel alternative in cases of PTSD refractory to current pharmacological treatments.

Keywords: Amygdala; Deep brain stimulation; Paroxetine; Posttraumatic stress disorder; Psychosurgery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Deep Brain Stimulation*
  • Disease Models, Animal
  • Male
  • Paroxetine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Uptake Inhibitors / pharmacology
  • Stress Disorders, Post-Traumatic / therapy*

Substances

  • Serotonin Uptake Inhibitors
  • Paroxetine