Extinction depends, at least partly, on new learning that is specific to the context in which it is learned. Several behavioral phenomena (renewal, reinstatement, spontaneous recovery, and rapid reacquisition) suggest the importance of context in extinction. The present article reviews research on the behavioral and neurobiological mechanisms of contextual influences on extinction learning and retrieval. Contexts appear to select or retrieve the current relationship of the conditional stimulus (CS) with the unconditional stimulus (US), and they are provided by physical background cues, interoceptive drug cues, emotions, recent trials, and the passage of time. The current article pays particular attention to the effects of recent trials and trial spacing. Control of fear extinction by physical context involves interactions between the dorsal hippocampus and the lateral nucleus of the amygdala. This interaction may be mediated by gamma-aminobutyric acid (GABA)-ergic and adrenergic mechanisms.

The formalin test is increasingly used as a model of injury-produced pain but there is no generally accepted method of pain rating. To examine the properties of various pain rating methods we established dose-response relations for formalin injected in the plantar surface of one hind paw, and the analgesic effects of morphine and amphetamine using the most frequently reported behavioural measures of pain (favouring, lifting, licking and flinching/shaking of the injured paw) and combinations of these. Licking, elevation and favouring of the injected paw showed a biphasic response at all formalin doses. Flinching varied in form across the time course of formalin, and the biphasic nature of the behaviour was not as apparent. In untreated rats all these behaviours were infrequent. Flinching and favouring were increased after injection of local anaesthetic into the paw but remained negligible relative to the effect of formalin. Grooming other than that directed to the injected paw was elevated in a dose-dependent manner by formalin. Intercorrelations between the behaviours were different for the initial response and the second phase. Correlational analysis indicated that no single behavioural measure was a strong predictor of formalin, morphine and amphetamine dose. A simple sum of time spent licking plus elevating the paw, or the weighted pain score of Dubuisson and Dennis (1977), were superior to any single measure (r ranging from 0.75 to 0.86). Addition of flinching and favouring to the combined pain score using multiple regression did not increase variance explained. Depending on the measure used, a sedative dose of pentobarbital produced apparent analgesia, hyperalgesia or no effect. The interphase depression of pain, as well as the analgesic effects of morphine and amphetamine, were all associated with increased motor activation. Power analysis indicated that using a moderate dose of formalin and a combined pain score gave the greatest power to detect differences in pain. It was also found that pain scores increase with ambient temperature and that rat strains may differ in formalin pain sensitivity.

Rats were subjected to one or two cycles of context fear conditioning and extinction to study the roles of the prelimbic cortex (PL) and infralimbic cortex (IL) in learning and relearning to inhibit fear responses. Inactivation of the PL depressed fear responses across the first or second extinction but did not impair learning or relearning fear inhibition (experiment 1). Inactivation of the IL did not affect inhibition across the first extinction but disrupted its long-term retention. Inactivation of the IL impaired inhibition across the second extinction, and inactivation before or after this extinction impaired long-term retention (experiments 2 and 3). Inactivation of the IL before the retention test restored extinguished fear responses (experiment 4). These results show for the first time that neuronal activity in the PL is involved in the expression of fear responses but not in the learning that underlies long-term fear inhibition. They also confirm that the IL is involved in this inhibitory learning: Specifically, they show that the IL is critical for consolidation and retrieval of this inhibitory learning. The role of the IL is discussed in terms of a contemporary neural model of fear extinction.Experimental extinction is widely used to study the neural substrates underlying the inhibition of Pavlovian conditioned fear responses. Extinction occurs when the signaling relation between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is broken by repeated exposures to the CS in the absence of the US. The fear responses (e.g., freezing, potentiated startle) produced by the signaling relation decline across the CS alone exposures and eventually cease to occur. Fear of the CS is said to be extinguished. A historically important explanation of extinction was that breaking the relation between the CS and US weakened and eventually erased the association formed by that relation (Rescorla and Wagner 1972). However, it is now clear that this explanation is at best incomplete. Various phenomena show that retraining the CS-US association is not necessary for the restoration of fear responses to an extinguished CS (Bouton et al. 2006). These phenomena include the ''renewal'' of fear responses when the CS is tested outside the context where extinction had occurred, the ''spontaneous recovery'' of such responses with the elapse of time since extinction, and the ''reinstatement'' of fear responses when the extinguished CS is tested in the presence of or shortly after exposure to danger. Such restoration phenomena show that at least some of the original association survives extinction in spite of the fact that the CS fails to elicit fear responding. This implies that extinction involves new learning which coexists with the old while inhibiting its expression in fear responses (Myers and Davis 2007;Quirk and Mueller 2008).

Four experiments studied contextual control over rats' freezing to conditioned stimuli (CSs) that had been paired with shock and were then extinguished. In Experiment 1, rats were exposed to a CS A-shock and a CS B-shock pairing in Context C. CS A was then extinguished in Context A, and CS B in Context B. Freezing was renewed when each CS was presented in the context where the other CS had been extinguished. In Experiments 2-4, rats were exposed to a CS A-shock pairing in A and a CS B-shock pairing in B. They were then exposed to Context C where one, both, or neither of the CSs were extinguished, or where both CSs continued to be reinforced. On test, the rats froze more to CS A than to CS B in Context A, and more to CS B than to CS A in Context B, but only if the CSs had been extinguished. Thus, after extinction, rats use contexts to regulate retrieval not only of their memory for extinction, but also of their memory for the original conditioning episode.

Six experiments used rats to study the effects of the beta-carboline FG 7142 on extinction of fear responses (freezing) to an auditory cue that had signalled footshock. Subcutaneous injection of FG 7142 interfered with the development of extinction without having any detectable effect on the rats' levels of fear prior to extinction. Injection of FG 7142 also reversed extinction, partially reinstating fear responses that had been extinguished previously. A similar reinstatement of extinguished fear was seen when rats were tested for fear of the cue in a different chamber. The reinstatement produced by FG 7142 and that caused by context shift were not additive: FG 7142 did not increase extinguished fear if rats were tested in the different chamber. Finally, FG 7142 had no detectable effect on the latent inhibition of fear produced by repeatedly presenting the cue alone before conditioning with shock, even though this inhibition, like extinction, was affected by a shift in context. The present findings indicate that GABA transmission at GABA(A) receptors is involved in the inhibition of extinguished fear, and that this effect of GABA is regulated by those cues that constitute the extinction context.

Three experiments used the freezing response of rats to examine the effects of pre-exposure to an environment upon (1) its associability with shock and (2) its discriminability from a second environment. Experiments 1 and 2 demonstrated that freezing was proportional to the interval between exposure to the environment at time T1 and the occurrence of shock at T2. This function was shifted by pre-exposure to the to-be-shocked environment, with brief pre-exposures increasing (facilitation) and extended pre-exposures decreasing (latent inhibition) the impact of a given T1-T2 interval on freezing. Experiment 3 provided evidence that the facilitatory and latent inhibitory effects resulting from brief and extended exposures to the to-be-shocked environment were accompanied by an increase in discriminability. The results were taken to have supported the claim that pre-exposure changes associability as well as discriminability (Hall & Honey, 1989) and were discussed in terms of the model for perceptual learning proposed by McLaren, Kaye, and Mackintosh (1990).

Rats exposed to a simultaneous compound of a flavor and sucrose subsequently exhibited a preference for the flavor over water. This preference persisted across repeated testing even though the flavor was presented in the absence of sucrose. The preference did, however, extinguish if the rats were hungry when trained or tested, or if they had been reexposed to sucrose between training and test. Though failing to extinguish the preference, presentation of the flavor outside the compound protected it from the effects of sucrose devaluation, indicating that these presentations extinguished the within-compound association between the flavor and sucrose. The authors conclude that the hedonic reaction elicited by sucrose imbues the flavor with the same hedonic properties, and these properties maintain the preference independently of the flavor-sucrose association.

No abstract