Theoretical mechanisms underlying the trial-spacing effect in Pavlovian fear conditioning.

Barela, Peter B.

doi:10.1037/0097-7403.25.2.177

Cited by 76 publications

(75 citation statements)

References 59 publications

(80 reference statements)

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“…One very general excitatory learning rule is that memory is stronger when training trials are "spaced" or distributed in time (Ebbinghaus 1885(Ebbinghaus /1913Carew and Kandel 1973;Fanselow and Tighe 1988;Fanselow et al 1993;Tully et al 1994;Kogan et al 1997;Freudenthal et al 1998;Barela 1999;Josselyn et al 2001). We recently reported that, in contrast to most acquisition learning, more short-and long-term extinction of cue fear followed temporally massed CS presentations than spaced presentations (Cain et al 2003).…”

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confidence: 99%

Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

Cain¹,

Blouin²,

Barad³

2004

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191

178

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Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS exposures trigger two opposing processes: (1) fear extinction, which is favored by CS massing, and (2) fear incubation (increase), which is favored by spacing. We here report the effects of manipulating the adrenergic system during massed or spaced CS presentations in fear-conditioned mice. We administered yohimbine (5 mg/kg), an ␣ 2 -receptor antagonist, or propranolol (10 mg/kg), a ␤-receptor antagonist, systemically prior to CS presentation sessions and recorded both short-and long-term changes in conditional freezing. Yohimbine treatment facilitated extinction of both cue and context fear with massed protocols. When given before spaced CS presentations, propranolol led to a persistent incubation of cue fear, whereas yohimbine led to persistent extinction, compared with vehicle-treated animals, which showed no change in fear. These results suggest that norepinephrine positively modulates the formation of fear extinction memories in mice. They also provide clear evidence that spaced CS presentations trigger both fear-reducing (extinction) and fear-increasing (incubation) mechanisms.

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confidence: 99%

Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

Cain¹,

Blouin²,

Barad³

2004

Learn. Mem.

191

178

View full text Add to dashboard Cite

show abstract

“…A very general excitatory learning rule is that memory is stronger when training trials are "spaced" or distributed in time (Ebbinghaus 1885(Ebbinghaus /1913Carew and Kandel 1973;Fanselow and Tighe 1988;Fanselow et al 1993;Tully et al 1994;Kogan et al 1997;Freudenthal et al 1998;Barela 1999;Josselyn et al 2001). We recently reported that, in contrast to most acquisition learning, more short-and long-term extinction of cue fear followed temporally massed CS presentations than spaced presentations (Cain et al 2003).…”

mentioning

confidence: 99%

Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice

Ponnusamy¹,

Nissim²,

Barad³

2005

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123

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Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized that blockade of D2 receptors might facilitate extinction in mice, while agonists should block extinction, as they do in rats. One day after fear conditioning mice with three pairings of a white noise conditional stimulus (CS) with moderate footshock, we injected the D2 antagonist, sulpiride, the D2 agonist, quinpirole, or vehicle, just before repeated CS presentations to generate extinction. We assayed fear by measuring behavioral freezing during extinction presentations and then drug-free during CS presentations 1 d later. We found that sulpiride injections before extinction training facilitated extinction memory 24 h later, while quinpirole partially blocked extinction memory compared with vehicle-injected controls. Notably, sulpiride treatment yielded significant extinction after spaced CS presentations, which yield no extinction at all in vehicle-treated mice. These findings suggest that dopamine D2-mediated signaling contributes physiological inhibition of extinction, and that D2 antagonists may be useful adjuncts to behavior therapy of human anxiety disorders.Extinction of conditioned fear in mammals is an important preclinical model of behavior therapy, one of the most effective treatments for human anxiety disorders (Wolpe 1969;Craske 1999). Despite the efficacy of behavior therapy for human anxiety disorders, extinction-like treatments require repeated cue exposures and are vulnerable to reversal by a number of environmental factors. Thus, a deeper understanding of the synaptic mechanisms of extinction may permit the development of adjunctive medications to facilitate extinction learning, and perhaps, to make it more permanent.Anxiety disorders affect about 16% of the American population and include panic disorder (PD, 1.7%), obsessivecompulsive disorder (OCD, 2.3%), post-traumatic stress disorder (PTSD, 3.6%), generalized anxiety disorder (GAD, 2.8%), social phobia (2%), and simple phobias (8%) (US-Surgeon-General 1999). The rate of PTSD may well go higher in the context of current wars and terrorist acts. Given the enormous burden of such anxiety disorders, we are fortunate in having a reasonable animal model for the acquisition of some of these fears, that is, classically conditioned fear, and an even better animal model of an effective treatment method for those disorders, extinction of conditioned fear.Pavlovian, or classical, fear conditioning has long been an important model both of associative learning and of the etiology of human anxiety (Watson and Rayner 1920;Eysenck 1979;Wolpe and Rowan 1988). Temporal pairing of a neutral conditional stimulus (CS) with an aversive unconditional stimulus (US) generates robust conditional fear responses upon subseque...

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“…There are a number of mechanisms that can contribute to the trial spacing effect in classical conditioning (see Barela, 1999, for one recent review). Interest in trial spacing has been renewed in recent years because of claims that the animal's perception of time is central to conditioning.…”

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confidence: 99%