Preventing Return of Fear in an Animal Model of Anxiety: Additive Effects of Massive Extinction and Extinction in Multiple Contexts

Abstract

Fear conditioning and experimental extinction have been presented as models of anxiety disorders and exposure therapy, respectively. Moreover, the return of fear serves as a model of relapse after exposure therapy. Here we present two experiments, with rats as subjects in a lick suppression preparation, in which we assessed the additive effects of two different treatments to attenuate the return of fear. First, we evaluated whether two phenomena known to generate return of fear (i.e., spontaneous recovery and renewal) summate to produce a stronger reappearance of extinguished fear. At test, rats evaluated outside the extinction context following a long delay after extinction (i.e., a delayed context shift) exhibited greater return of extinguished fear than rats evaluated outside the extinction context alone, but return of extinguished fear following a delayed context shift did not significantly differ from the return of fear elicited in rats tested following a long delay after extinction alone. Additionally, extinction in multiple contexts and a massive extinction treatment each attenuated the strong return of fear produced by a delayed context shift. Moreover, the conjoint action of these treatments was significantly more successful in preventing the reappearance of extinguished fear, suggesting that extensive cue exposure administered in several different therapeutic settings has the potential to reduce relapse after therapy for anxiety disorders, more than either manipulation alone.

Behavioral techniques for attenuating the expression of fear associations in an animal model of anxiety

“…Laborda and Miller (2013) replicated and extended Denniston et al’s (2003) protective effect of massive numbers of extinction trials and Gunther et al’s (1998) protective effect of extinction being administered in multiple contexts, in a preparation in which spontaneous recovery and renewal otherwise summated to produce strong return of fear of the CS (see Rosas & Bouton, 1998; Rosas, Vila, Lugo, & López, 2001). They found that extended extinction treatment in multiple contexts was more effective in attenuating the return of fear than each of these techniques by itself.…”

“…For example, the return of fear has been attenuated in our fear-conditioning preparation with rats as experimental subjects by: a) using a massive number of extinction trials (Denniston, Chang, & Miller, 2003), b) delivering extinction treatment in multiple contexts (Gunther, Denniston, & Miller, 1998), c) spacing the extinction trials (Urcelay, Wheeler, & Miller, 2009), and d) spacing the extinction sessions (Laborda, Miguez, & Miller, 2014). Moreover, Laborda et al (2014) provided evidence suggesting that the mechanisms underlying the effects of session spacing are different from those of trial spacing.…”

Can fear extinction be enhanced? A review of pharmacological and behavioral findings

“…Another rat study concluded that massed extinction trials produce better short-term but worse long-term loss of context-conditioned fear responses than spaced trials (Li and Westbrook, 2008). A more recent study found that massed extinction treatment in rats attenuated the strong renewal of fear induced by a delayed interval between extinction and test (Laborda and Miller, 2013). In mice, both short-term and long-term fear extinction was greater with temporally massed presentations of the CS than spaced ones, where this finding may be the opposite of that for fear acquisition (Cain et al, 2003).…”

“…Extinction in multiple contexts and a massed extinction treatment each attenuated the strong return of fear produced by testing long after extinction, and the two treatments interacted to further minimize return of fear (Laborda and Miller, 2013). However, another rat study found that extinction in multiple contexts did not reduce the size of the final renewal effect, upon testing in a new context (Bouton et al, 2006a).…”

Reinstauración de la tolerancia al etanol: la función del contexto

“…Al clasificar la reinstauración como un fenómeno de recuperación de respuestas se podría hipotetizar que manipulaciones que pueden prevenir otros fenómenos de recuperación también podrían afectar la reinstauración. Se ha señalado, por ejemplo, que la renovación se ve retardada si es que la extinción es llevada a cabo en múltiples contextos (e.g., Chelonis, Calton, Hart y Schachtman, 1999;Glautier, Elgueta, y Nelson, en prensa;Gunther, Denniston y Miller 1998;pero ver Betancourt, Corada et al, 2008;Bouton, García-Gutiérrez, Zilski, y Moody, 2006), o si se realizan ensayos masivos de extinción (e.g., Denniston, Chang y Miller, 2003;, o si la extinción se realiza en presencia de múltiples claves (Glautier y Elgueta, 2009), o si los ensayos y sesiones de extinción se distribuyen en el tiempo (e.g., Laborda, Miguez y Miller, 2013;Miguez, Witnauer, Laborda y Miller, en prensa;Urcelay, Wheeler y Miller, 2009; para una revisión de esta y otras estrategias para prevenir recaídas ver Laborda, McConnell y Miller, 2011). En la actualidad pocos estudios se han enfocado a la reducción del fenómeno de reinstauración.…”