Early fear as a predictor of avoidance in a rat model of post-traumatic stress disorder

Exposure of humans and animals to an intensely fearful experience can lead to an enduring behavioral profile involving fear and avoidance. The present study examined if rats that show more fear to a novel tone one day after exposure to footshocks exhibit more avoidance-like responses over a 4-week period. Rats were exposed to an episode of moderately intense footshock (5 x 2s episodes of 1.5 mA presented randomly over 3 min). Shock rats that exhibited a high level of fear (HR) to a novel tone one day after the shock exposure showed more avoidance of open spaces and novel rats when compared to shock rats that exhibited a lower level of fear to the novel tone (LR). Similarly, HR emitted more ultrasonic vocalization in the dysphoric range (20-30 kHz) when placed in a novel chamber or the chamber in which shock was given. This study highlights the importance of early fear as a contributing factor for the development of lasting changes in avoidance. These results also support the view that the presence of an intense peritraumatic stress response may be a predictor of the subsequent development of a lasting negative emotional state in humans exposed to trauma. (C) 2011 Elsevier B.V. All rights reserved

Orexins in the midline thalamus are involved in the expression of conditioned place aversion to morphine withdrawal

Previous studies have implicated the bed nucleus of the stria terminalis, central nucleus of the amygdala and the shell of the nucleus accumbens (collectively called the extended amygdala) as playing an important role in mediating the aversive emotion associated with opioid withdrawal. The paraventricular nucleus of the thalamus (PVT) provides a very dense input to the extended amygdala, and the PVT is densely innervated by orexin neurons, which appear to be involved in producing some of the physical and emotional effects associated with morphine withdrawal. In the present study, we confirm that the PVT is densely innervated by orexin fibers, whereas the regions of the extended amygdala associated with the effects of morphine withdrawal are poorly innervated. Microinjections of the orexin-1 receptor (OX1R) antagonist SB334867 or the orexin-2 receptor (OX2R) antagonist TCSOX229 at doses of 5.0 or 15.0 mu g into the PVT region did not affect the acquisition of the conditioned place aversion (CPA) nor the physical effects produced by naloxone-precipitated morphine withdrawal. In contrast, microinjections of TCSOX229 (15.0 mu g) in the PVT region significantly attenuated the expression of naloxone-induced CPA while microinjections of SB334867 at the same dose had no effect. The results from these experiments indicate a role for OX2R in the PVT on the expression of CPA associated with morphine withdrawal. Orexins may mediate the aversive effects of morphine withdrawal by engaging the extended amygdala indirectly through the action of orexins on the PVT. (C) 2010 Elsevier Inc. All rights reserved