Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Abstract

Oxytocin reportedly decreases anxious feelings in humans and may therefore have therapeutic value for anxiety disorders, such as post-traumatic stress disorder (PTSD). As PTSD patients have exaggerated startle responses, a fear-potentiated startle paradigm in rats may have face validity as an animal model to examine the efficacy of oxytocin in treating these symptoms. Oxytocin (0, 0.01, 0.1, or 1.0 mg, subcutaneously) was given either 30 min before fear conditioning, immediately after fear conditioning, or 30 min before fear-potentiated startle testing to assess its effects on acquisition, consolidation, and expression of conditioned fear, respectively. Startle both in the presence and absence of the fear-conditioned light was significantly diminished by oxytocin when administered at acquisition, consolidation, or expression. There was no specific effect of oxytocin on light fear-potentiated startle. In an additional experiment, oxytocin had no effects on acoustic startle without previous fear conditioning. Further, in a context-conditioned test, previous light-shock fear conditioning did not increase acoustic startle during testing when the fear-conditioned light was not presented. The data suggest that oxytocin did not diminish cue-specific conditioned nor contextually conditioned fear, but reduced background anxiety. This suggests that oxytocin has unique effects of decreasing background anxiety without affecting learning and memory of a specific traumatic event. Oxytocin may have antianxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in PTSD patients.

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

“…A Dunnet's test background anxiety scores revealed significant differences between saline compared with oxytocin 0.01 mg/kg (po0.036) and saline compared with oxytocin 0.1 mg/kg (po0.042). Collectively, these results indicate that systemically administered oxytocin reduces background anxiety, an enhancement of startle to the noise alone that occurs following fear conditioning (Missig et al, 2010).…”

“…This effect is different from other anti-anxiety compounds, which markedly reduce startle during the fearconditioned stimulus (CS), yet leave startle in the absence of the CS unaffected (Davis et al, 1993). A series of follow-up experiments revealed that this reduction of background anxiety by oxytocin is likely not due contextual conditioning or a reduction in the ability to startle (Missig et al, 2010). This background anxiety may be similar to increased startle responses to unsignaled, unexpected startle stimuli observed in panic and post-traumatic stress disorder patients (Grillon, 2002).…”

“…pre-fear startle occurs before both fear conditioning and oxytocin administration. Cue-specific fear-potentiated startle is the increase in startle amplitude in the light + noise trials compared with the startle amplitude in the noise trials during the fear-potentiated startle test (adapted from Missig et al, 2010).…”

“…Recently our lab has used a rodent fear-potentiated startle paradigm to test the effects of systemic oxytocin on fear and anxiety behavior (Missig et al, 2010). Fear-potentiated startle paradigms are used to probe the internal emotional state of animals and humans (Davis and Whalen, 2001;Grillon and Baas, 2003), and have substantial humananimal translational validity and relevance for anxiety disorders (Davis et al, 2010;Grillon and Baas, 2003).…”

Anti-stress Effect of Hypothalamic Oxytocin, Importance of Somatosensory Stimulation and Social Buffering

“…Increased OXT neurotransmission during traumatic events is likely to prevent the formation of aversive memories. When OXT is centrally administered prior to fear conditioning or extinction training, fear expression and facilitated fear extinction are decreased in rats [31] .…”