Sign-tracking to an appetitive cue predicts incubation of conditioned fear in rats

Abstract

Although post-traumatic stress disorder (PTSD) and addiction are very different disorders, both are characterized by hyperreactivity to trauma- or drug-related cues, respectively. We investigated whether an appetitive conditioning task, Pavlovian conditioned approach, which predicts vulnerability to reinstatement of cocaine-seeking, also predicts fear incubation, which may be a marker for vulnerability to PTSD. We classified rats based on whether they learned to approach and interact with a food predictive cue (sign-trackers), or, whether upon cue presentation they went to the location of impending food delivery (goal-trackers). Rats were then exposed to extensive Pavlovian tone-shock pairings, which causes the fear response to increase or “incubate” over time. We found that the fear incubation effect was only present in sign-trackers. The behavior of goal-trackers was more consistent with a normal fear response – it was most robust immediately after training and decayed slowly over time. Sign-trackers also had lower levels of brain-derived neurotrophic factor (BDNF) protein in the prefrontal cortex than goal-trackers. These results indicate that, while many factors likely contribute to the disproportionate co-occurrence of PTSD and substance abuse, one such factor may be a core psychological trait that biases some individuals to attribute excessive motivational significance to predictive cues, regardless of the emotional valence of those cues. High levels of BDNF in the prefrontal cortex may be protective against developing excessive emotional and motivational responses to salient cues.

Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues

“…From another perspective, the heightened mesolimbic response to cues in a subset of our clinical population also has parallels to findings in the pre-clinical literature on incentive salience (Robinson & Berridge 1993). A subgroup of individuals (‘sign-trackers’) in the general population are more responsive to signals for reward (Flagel et al 2010) even without prior stress; these results have recently been extended to the aversive domain (Morrow, Maren, & Robinson 2011; Morrow et al 2015). These two viewpoints (evolutionary and incentive salience) may actually be complementary, in that a subgroup of individuals could be inherently more cue-reactive, but a history of stress or abuse may enhance or even create this vulnerability (Lomanowska et al 2011).…”

Rats that sign-track are resistant to Pavlovian but not instrumental extinction

“…This may have implications for the treatment of disorders characterized by hypersensitivity to reward cues, such as obesity and addiction (Berridge 2009; Robinson and Berridge 2008), and perhaps traumatic cues as well (Morrow et al 2011; Morrow et al 2014). The ability of cues to trigger excessive motivation for food or drugs is well established (Everitt and Robbins 2005; Robinson and Berridge 2008; Stewart et al 1984).…”

Pavlovian Conditioned Approach Training in Rats

“…For example, STs are more vulnerable to cued fear expression 27 and show incubation of cued fear following extended fear conditioning 28 . Therefore, PCA procedures can be used to model individual variation in cue-directed behavior that may have relevance for multiple neuropsychiatric disorders and even comorbid disorders (e.g., addiction and posttraumatic stress disorder).…”