Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear

Abstract

Fear conditioning and fear extinction play key roles in the development and treatment of anxietyrelated disorders, yet there is little information concerning experiential variables that modulate these processes. Here we examined the impact of exposure to a stressor in a different environment on subsequent fear conditioning and extinction, and whether the degree of behavioral control that the subject has over the stressor is of importance. Rats received a session of either escapable (controllable) tailshock (ES), yoked inescapable (uncontrollable) tailshock (IS), or control treatment (HC) 7 days before fear conditioning in which a tone and footshock were paired. Conditioning was measured 24 h later. In a second experiment rats received ES, IS or HC 24 h after contextual fear conditioning. Extinction then occurred every day beginning 7 days later until a criterion was reached. Spontaneous recovery of fear was assessed 14 days after extinction. IS potentiated fear conditioning when given before fear conditioning, and potentiated fear responding during extinction when given after conditioning. Importantly, ES potently interfered with later fear conditioning, decreased fear responding during fear extinction, and prevented spontaneous recovery of fear. Additionally, we examined if the activation of the ventral medial prefrontal cortex (mPFCv) by ES is critical for the protective effects of ES on later fear conditioning. Inactivation of the mPFCv with muscimol at the time of the initial experience with control prevented ES-induced reductions in later contextual and auditory fear conditioning.Finally, we explored if the protective effects of ES extended to an unconditioned fear stimulus, ferret odor. Unlike conditioned fear, prior ES increased the fear response to ferret odor to the same degree as did IS.Keywords stressor controllability; medial prefrontal cortex; fear conditioning; fear extinction; spontaneous recovery; PTSD The phenomena of Pavlovian fear conditioning and fear extinction have come to be viewed as key processes involved in the development (Mineka and Zinbarg, 2006) and treatment (Rothbaum and Davis, 2003) of anxiety disorders, respectively. In addition to the obvious procedural similarity between fear conditioning/extinction and the conditions that foster Address correspondence to Michael V. Baratta,

The STRONG STAR Multidisciplinary PTSD Research Consortium

“…For example, rodents exposed to inescapable tail shock display less aggression in a shock-elicited aggression test (similar to our finding of reduced active burying in the shock-probe defensive burying test) and reduced intruder attack by alpha males (Maier, 1984). These rats also display cognitive deficits, including more errors in tests involving learning contingencies (Maier, 1984) and delayed contextual fear extinction (Baratta et al, 2007). Again, this is similar to our previous finding that CAPS treatment impaired fear extinction.…”

Acute nicotine enhances spontaneous recovery of contextual fear and changes c-fos early gene expression in infralimbic cortex, hippocampus, and amygdala

“…Spontaneous recovery was expressed as percent rebound to the freezing levels measured during initial testing (%Rebound; average freezing during retesting × 100/average freezing during initial testing; Santini et al 2001). Following studies examining recovery of conditioned behavior such as freezing, fear potentiated-startle, and drug self-administration (e.g., Morgan et al 1993;Corcoran et al 2005;Norrholm et al 2006;Baratta et al 2007;Wing and Shoaib 2008), an extinction criterion was employed to ensure successful extinction learning. Specifically, animals that did not show freezing levels below 30% of their initial freezing levels at the end of the extinction phase were removed from analysis as freezing levels above this level may indicate incomplete extinction.…”

The role of prior stressor controllability and the dorsal raphé nucleus in sucrose preference and social exploration

“…For the IS subject turning the wheel has no effect. Exposure to IS produces behavioral sequelae that do not follow ES [5,26,43,44]. Consequences of stress that are unique to IS have been extensively reviewed [15,29,35,43] and called "learned helplessness effects" [26].…”