Effects of extinction treatments on the reduction of conditioned responding and conditioned hyperarousal in a rabbit model of posttraumatic stress disorder (PTSD)

Abstract

We have previously characterized a model of posttraumatic stress disorder (PTSD), based on classical conditioning of the rabbit nictitating membrane response (NMR), that focuses on 2 key PTSD-like features: conditioned responses to trauma-associated cues and hyperarousal. In addition to the development of conditioned NMRs (CRs) to a tone conditioned stimulus (CS) associated with a periorbital shock unconditioned stimulus (US), we have observed that rabbits also exhibit a conditioning-specific reflex modification (CRM) of the NMR that manifests as an exaggerated and more complex reflexive NMR to presentations of the US by itself, particularly to intensities that elicited little response prior to conditioning. Previous work has demonstrated that unpaired presentations of the CS and US are successful at extinguishing CRs and CRM simultaneously, even when a significantly weakened version of the US is utilized. In the current study, additional extinction treatments were tested, including continued pairings of the CS with a weakened US and exposure to the training context alone, and these treatments were contrasted with the effects of unpaired extinction with a weakened US and remaining in home cages with no further treatment. Results showed that continued pairings only slightly decreased CRs and CRM, while context exposure had no effect on CRs and marginal effects on reducing CRM. Unpaired extinction was still the most effective treatment for reducing both. Findings are discussed in terms of applications to cognitive-behavioral therapies for treatment of PTSD, such as incorporating mild, innately stressful stimuli into virtual reality therapy.

Figure 1

The mean percentage (± SEM) of CRs to the tone CS during 6 daily sessions of delay conditioning, 6 sessions of extinction, and a CR retention test consisting of CS-alone presentations (CS test). The right inset panel shows the first and last block of 10 trials for the CS test. During extinction, rabbits received either continued pairings of the CS with a weak shock US (PD, solid circle), exposure to the training context with no stimulus presentations (CTX, square), unpaired extinction with a weak US (UP, open circle), or remained in home cages (ØEXT, triangle). Data during extinction are pictured only for groups receiving CS presentations (PD, UP).

Figure 2

Averaged response topographies for the unconditioned response to the periorbital shock US during the first 20 trials of the US pretest (Pretest, dotted black line), the US posttest following delay conditioning (Post1, red line), and the US posttest following extinction (Post2, blue line) during which rabbits received either continued pairings of the CS with a weak shock US (PD, top left), exposure to the training context with no stimulus presentations (CTX, top right), unpaired extinction with a weak US (UP, bottom right), or remained in home cages (ØEXT, bottom left). Topographies are shown at the five US intensities (2.0, 1.0, 0.5, 0.25, 0.1 mA) presented during US testing, collapsed across duration.

Figure 3

Mean (± SEM) % URs (left column), magnitude of the UR amplitude (mAmp, middle column), and magnitude of the UR area (mArea, right column) for the first 20 trials of presentations of the periorbital shock US during pretest (Pretest, white bar), the posttest following delay conditioning (Post1, black bar), and the posttest following extinction (Post2, gray bar) during which rabbits received either continued pairings of the tone CS with a weak US (PD, top row), exposure to the training context with no stimulus presentations (CTX, 2nd row from top), unpaired extinction with a weak US (UP, bottom row), or remained in home cages (ØEXT, 2nd row from bottom). Bar graphs are shown for the five US intensities (0.1, 0.25, 0.5, 1.0, 2.0 mA) presented during US testing, collapsed across duration.