Renewal and spontaneous recovery, but not latent inhibition, are mediated by gamma-aminobutyric acid in appetitive conditioning.

Previous research has reported a role for the neurotransmitter gamma-aminobutyric acid (GABA) in the extinction and renewal of conditioned fear. Here, the authors examine whether GABA is involved in the acquisition, extinction, renewal, spontaneous recovery, and latent inhibition of appetitive conditioning. Using Long-Evans rats, systemic injection of the GABA A receptor inverse agonist FG 7142 was shown to eliminate ABA renewal (Experiment 1) and spontaneous recovery (Experiment 4) of appetitive responding by selectively reducing the recovery of extinguished magazine approach. Furthermore, treatment with FG 7142 had no effects on acquisition or single-session extinction (Experiment 3) or on the context-specific expression of latent inhibition (Experiment 2). These data suggest that ABA renewal and spontaneous recovery, but not latent inhibition or responding during acquisition and an initial extinction session, are mediated by GABAergic mechanisms in appetitive Pavlovian conditioning. They provide support for the view that renewal and spontaneous recovery share a common psychological mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of FG7142 on two types of forgetting in 18-day-old rats.

The authors studied the role of gamma-aminobutyric acid (GABA) in 2 types of forgetting of fear in the developing rat. One type of forgetting studied was that observed after an intermediate retention interval (the "Kamin effect"); the other type studied was that observed after a longer interval (infantile amnesia). Rats were given pairings of an auditory conditioned stimulus with shock, and learned fear was assessed by freezing. Forgetting at an intermediate retention interval (1 hr) was not alleviated by the GABAA receptor partial inverse agonist FG7142 (0, 1, 5, or 10 mg/kg), whereas forgetting at a longer retention interval (48 hr) was alleviated. These results suggest that in the developing rat, forgetting observed at different retention intervals is mediated by different physiological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A developmental dissociation of context and GABA effects on extinguished fear in rats.

Although extinction has attracted considerable attention in recent years, there has been very little empirical work on extinction during development. Using Pavlovian fear conditioning, the authors provide evidence for developmental differences in extinction. Specifically, Postnatal Day (PND) 23 rats exhibited recovery of an extinguished freezing response to an auditory conditioned stimulus when tested in a context different from that in which extinction occurred (i.e., renewal) or when injected with the gamma-amino butyric acid (GABA) inverse agonist FG7142 prior to test. In contrast, PND 16 rats failed to exhibit either of these effects, although a subsequent experiment demonstrated that FG7142 alleviated spontaneous forgetting in PND 16 rats. Taken together, it appears that there are fundamental differences in the processes involved in extinction across development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D-cycloserine facilitates extinction but does not eliminate renewal of the conditioned emotional response.

The effect of D-cycloserine (DCS), an NMDA partial agonist, on extinction of fear was investigated in rats using the conditioned emotional response preparation. Fear extinction was facilitated when the first 4 trials occurred with a 30-mg/kg dose of DCS. However, extinguished fear was "renewed" regardless of the drug treatment when the rats were returned to the context in which fear had been conditioned. Additional results suggest that DCS's facilitation of extinction is a small but meaningful effect in the current method. The results suggest caution regarding the use of DCS as an adjunct to extinction: Although the drug may modestly facilitate extinction learning, it does not necessarily destroy the potential for relapse. Behavioral mechanisms are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed extinction attenuates conditioned fear renewal and spontaneous recovery in humans.

This study investigated whether the retention interval after an aversive learning experience influences the return of fear after extinction training. After fear conditioning, participants underwent extinction training either 5 min or 1 day later and in either the same room (same context) or a different room (context shift). The next day, conditioned fear was tested in the original room. When extinction took place immediately, fear renewal was robust and prolonged for context-shift participants, and spontaneous recovery was observed in the same-context participants. Delayed extinction, by contrast, yielded a brief form of fear renewal that reextinguished within the testing session for context-shift participants, and there was no spontaneous recovery in the same-context participants. The authors conclude that the passage of time allows for memory consolidation processes to promote the formation of distinct yet flexible emotional memory traces that confer an ability to recall extinction, even in an alternate context, and minimize the return of fear. Furthermore, immediate extinction can yield spontaneous recovery and prolong fear renewal. These findings have potential implications for ameliorating fear relapse in anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of D-cycloserine on the extinction of appetitive operant learning.

Four experiments with rat subjects examined whether D-cycloserine (DCS), a partial NMDA agonist, facilitates the extinction of operant lever-pressing reinforced by food. Previous research has demonstrated that DCS facilitates extinction learning with methods that involve Pavlovian extinction. In the current experiments, operant conditioning occurred in Context A, extinction in Context B, and then testing occurred in both the extinction and conditioning contexts. Experiments 1A and 1B tested the effects of three doses of DCS (5, 15, and 30 mg/kg) on the extinction of lever pressing trained as a free operant. Experiment 2 examined their effects when extinction of the free operant was conducted in the presence of nonresponse-contingent deliveries of the reinforcer (that theoretically reduced the role of generalization decrement in suppressing responding). Experiment 3 examined their effects on extinction of a discriminated operant, that is, one that had been reinforced in the presence of a discriminative stimulus, but not in its absence. A strong ABA renewal effect was observed in all four experiments during testing. However, despite the use of DCS doses and a drug administration procedure that facilitates the extinction of Pavlovian learning, there was no evidence in any experiment that DCS facilitated operant extinction learning assessed in either the extinction or the conditioning context. DCS may primarily facilitate learning processes that underlie Pavlovian, rather than purely operant, extinction. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Recovery of fear memories in rats: Role of gamma-amino butyric acid (GABA) in infantile amnesia.

Infantile amnesia is a ubiquitous phenomenon, but its neural bases remain largely unknown. The authors identify a role for GABAergic transmission in suppressing retrieval of memories acquired in infancy. Eighteen-day-old rats received pairings of white noise and shock; considerable forgetting of this experience (assessed by freezing) occurred after 10 days. The memory was recovered by pretest administration of the GABAA inverse agonist FG7142 10 days, but not 2 months, after training. This effect of FG7142 generalized when a passive avoidance procedure was used. Also, FG7142 decreased fear of a latently inhibited conditioned stimulus, showing that the observed memory recovery effect was not due to a state-dependent process. It appears that GABA may be involved in infantile amnesia regardless of the emotional content of the memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Massed extinction trials produce better short-term but worse long-term loss of context conditioned fear responses than spaced trials.

A series of experiments studied the effects of the interval between extinction trials on the loss of context conditioned freezing responses. Rats were shocked in one context (A) but not in another (B) and subjected to extinction trials in context A. In Experiment 1, massed trials produced more rapid loss than spaced trials. A shift from spaced to massed trials maintained this loss, but the shift from massed to spaced trials restored lost responses. Experiments 2-5 examined this effect of massed trials on responding across spaced trials. They provided evidence that (a) a single trial was as effective as multiple daily massed trials, (b) learning occurred on the first of the massed trials but not on later ones, and (c) the first trial reduced the amount learned across subsequent massed trials. Finally, alternating extinction trials in A and B produced more response loss across spaced trials than blocks of trials in A and B. The results were discussed in terms of the role accorded to self-generated priming in the models developed by A. R. Wagner (1978, 1981). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of FG7142 on overexpectation of Pavlovian fear conditioning.

Six experiments studied the role of GABAA receptor activation in expression of overexpectation of Pavlovian fear conditioning. After separate pairings of CSA and CSB with shock in Stage I, rats received pairings of the compound AB with shock in Stage II, producing overexpectation of fear. The expression of overexpectation was attenuated, in a dose-dependent manner, by the benzodiazepine partial inverse agonist FG7142. FG7142 had no effect on responding to a CS paired with a low magnitude US or a CS subjected to associative blocking. These results suggest that the negative prediction error generated during overexpectation training may impose a mask on fear rather than erasing the original fear learning. They support claims that overexpectation shares features with extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A short intertrial interval facilitates acquisition of context-conditioned fear and a short retention interval facilitates its expression.

Rats were shocked in a context on two occasions and then tested for fear reactions as indexed by freezing. Rats spent the interval between conditioning trials and between conditioning and test in their home cages. A short interval between context-conditioning trials or between trials involving a discrete conditioned stimulus (CS) produced better learning than longer intervals. A short retention interval between conditioning and test produced better performance than longer intervals. The effects of the intertrial interval on learning are the opposite of those reported previously and are opposite to those predicted by contemporary learning theories. The effects of the training to test interval on performance are predicted by Wagner's sometimes opponent process (SOP) theory (Wagner, 1981). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms of resurgence of an extinguished instrumental behavior.

Four experiments examined “resurgence” of an instrumental behavior after extinction. All experiments involved three phases in which rats were (1) trained to press one lever for food reward, (2) trained to press a second lever while the first leverpress was extinguished, and (3) tested under conditions in which neither leverpress was rewarded. In each experiment, the first leverpress recovered (resurged) in Phase 3, when the second leverpress was extinguished. The results demonstrated that resurgence occurred when the schedules of reinforcement employed in Phases 1 and 2 yielded either an upshift, downshift, or no change in the rate of reward delivery between those phases. They also demonstrated that initial training on the first lever was required to observe a robust increase in pressing at test (resurgence is thus an associative effect). Resurgence was shown to occur over a wide variety of schedules of reinforcement in Phase 2 (including ratio, interval, and leverpress-independent schedules). Finally, the results do not support the view that resurgence occurs because response competition suppresses leverpressing of the first lever during extinction. Overall, they are consistent with the view that resurgence is a renewal effect in which extinction of an instrumental behavior is specific to the context provided by rewarded leverpressing during the extinction phase. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extinction, renewal, and spontaneous recovery of a spatial preference in the water maze.

Four experiments with C57BL/6 mice investigated extinction of a spatial preference in the Morris water maze. In Experiment 1, a spatial preference was extinguished by exposing mice to the water maze in the absence of a platform but in the presence of the distal spatial cues. In Experiment 2, extinction occurred when the platform was removed from the pool, when it was presented in random locations, or when it was presented consistently in the opposite location. Contextual renewal (Experiment 3) and spontaneous recovery (Experiment 4) of spatial preferences argue against an interpretation of extinction in terms of unlearning and instead suggest that extinction in the water maze, like extinction in Pavlovian conditioning, suppresses the original association. Implications of these findings for theories of spatial learning and hippocampal function are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blood donation is an act of benevolence rather than altruism.

Objectives: Blood donation is described as an archetypal altruistic behavior, and recruitment/retention campaigns emphasize altruism. Here, a benevolence hypothesis for blood donation (both the donor and recipient benefit) rather than the altruism hypothesis (only the recipient gains) is proposed. Design: Three United Kingdom-based studies contrasted benevolence and altruism: (a) a 6-month prospective study of blood donor behavior (Study 1: N = 957), (b) a cross-sectional study of blood donors' intentions (Study 2: N = 333), and (c) an experimental study examining the effect of benevolent and altruistic messages on willingness to help across high- and low-cost helping behaviors for committed and noncommitted blood donors (Study 3: N = 200). Main Outcome: Donor behavior and intentions-willingness. Measures: Beliefs in personal and societal benefit (Time 1) and actual donations (Time 2) were assessed in Study 1; beliefs in benevolence, altruism, hedonism, and kinship along with donation intentions were assessed in Study 2; and empathy, donor commitment, and willingness to donate blood, money, fund-raise, and staff a telephone helpline were assessed in Study 3. Results: Beliefs in personal rather than societal benefit predicted actual future donation. A path model showed that only beliefs in benevolence were associated with intentions to donate. Committed blood donors were more willing to donate blood when exposed to a benevolent message rather than an altruistic one. This effect was not observed for other forms of helping. Conclusions: The benevolence hypothesis is supported, suggesting that blood donor motivation is partly selfish. Blood donation campaigns should focus on benevolent rather than purely altruistic messages. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Persistence of conditioned flavor preferences is not due to inadvertent food reinforcement.

Almond preferences were produced by giving rats a mixture of almond and sucrose (Experiments 1-4) or saccharin (Experiment 4). A subsequent extinction procedure consisted of either repeated 2-bottle almond versus water tests (Experiment 1) or repeated exposure to almond alone (Experiments 2-4). The main independent variable was whether access to food following a session was given immediately, 30 min later, or 120 min later. No effect of extinction was found in any experiment. An important finding was that varying the delay until food access had no detectable effect. It was concluded that inadvertent flavor-food associations do not maintain preference for the flavor under extinction conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of training intertrial interval on acquisition of trace and long-delay fear conditioning in rats.

Many factors govern conditioning effectiveness, including the intertrial interval (ITI) used during training. The present study systematically varied the training ITI during both trace and long-delay fear conditioning. Rats were trained using one of six different ITIs and subsequently tested for conditioning to the white noise conditioned stimulus (CS) and the training context. After trace conditioning, percent freezing to the CS was positively correlated with training ITI, whereas percent freezing to the context was negatively correlated with training ITI. In contrast, when rats were trained using a long-delay paradigm, freezing during the CS test session did not vary as a function of training ITI; rats exhibited robust freezing at all ITIs. The long-delay conditioned rats exhibited relatively low levels of freezing during the context test. Thus, trace is more sensitive than long-delay fear conditioning to variations in the training ITI. These data suggest that training ITI is an important variable to consider when evaluating age or treatment effects, where the optimal ITI may vary with advancing age or pharmacological treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An experimental analysis of steady-state response rate components on variable ratio and variable interval schedules of reinforcement.

Three experiments explored a novel approach to analyzing the different components of response rate that are produced by exposure to free-operant schedules of reinforcement. It has been suggested that overall response rate comprises a tendency to initiate responding, and to continue to respond once the bout is initiated. Previous post hoc analyses of interresponse times (IRT) data have suggested several features of these different aspects of responding that the current experimental procedure broadly confirmed. Increasing the size of a variable interval (VI) schedule decreases the number of “burst-initiation” responses, but has less effect on responding once the burst has been initiated (Experiment 1); that the major difference between a variable ratio (VR) schedule and a VI schedule, is not in the number of “burst-initiation” responses, but in the number of “within-burst” responses, with shorter interresponse times that are emitted, with greater numbers of such “within-burst” responses being emitted on a VR schedule (Experiments 2 and 3). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of yohimbine on the extinction of conditioned fear: A role for context.

Six experiments with rat subjects examined the effect of yohimbine, an alpha-2 adrenergic autoreceptor antagonist, on the extinction of conditioned fear to a tone. Experiments 1 and 2 demonstrated that systemic administration of yohimbine (1.0 mg/kg) facilitated a long-term decrease in freezing after extinction, and this depended on pairing drug administration with extinction training. However, Experiments 3 and 4 demonstrated that yohimbine did not eradicate the original fear learning: Freezing was renewed when the tone was tested outside of the extinction context. Experiments 5 and 6 found that the contextually specific attenuation of fear produced by yohimbine transferred to another extinguished conditional stimulus (CS) and not to a nonextinguished CS. The results suggest that yohimbine, when administered in the presence of a neutral context, creates a form of inhibition in that context that allows that specific context to reduce fear of an extinguished CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Trial spacing is a determinant of cue interaction.

Four conditioned lick suppression experiments with rats examined the effect of trial spacing on cue interaction. Experiments 1 and 2 found overshadowing to be eliminated with massed compound stimulus- outcome pairings and the usual trial spacing effect to be reversed with compound acquisition trials. Experiment 3 found that whether acquisition compound- outcome pairings were massed or spaced determined the effect of posttraining extinction treatment. Extinction of the overshadowing cue reduced responding following massed training and increased responding following spaced training. Extinction of the context decreased responding following massed training. Experiment 4 found the conditioning and devaluation results to be associative and stimulus specific. These results are in accord with the extended comparator hypothesis (J. C. Denniston, H. I. Savastano, & R. R. Miller, 2001). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Familiarity-based stimulus generalization of conditioned suppression in rats is dependent on the perirhinal cortex.

We report that bilateral, excitoxic lesions of the perirhinal cortex attenuate rats' familiarity-based stimulus generalization. After surgery, rats were preexposed either to 2 auditory stimuli (A and B) or to only 1 auditory stimulus (B). Following preexposure, all rats received pairings of A and a footshock before assessment of generalized responding (conditioned suppression) to B. Sham rats' generalization was greater when preexposure was to both A and B than when preexposure was to B only. That pattern was abolished in lesioned rats, though no general deficiency was found in other measures of auditory processing. Our findings suggest that the perirhinal cortex is required for rats to encode familiarity as part of stimulus representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interdose interval effects on the development of contextual tolerance to nicotine's analgesic effects in rats (Rattus norvegicus).

Learning models of associative and nonassociative drug tolerance predict that the development of contextual tolerance to drug effects is disrupted when the drug is delivered at short interdose intervals (IDIs). The authors examined the impact of 1 long IDI and 2 short IDIs in the development of contextual nicotine tolerance. Associative tolerance was investigated by giving rats (Rattus norvegicus) 10 subcutaneous injections of nicotine at either long (72-hr) IDIs or short (6-hr and 4.5-hr) IDIs. The delivery of nicotine was either explicitly paired or explicitly unpaired with a distinctive context. A 3rd group of rats was exposed to the experimental procedures but received only saline. Associative tolerance to nicotine's analgesic effects was defined as a shift to the right of the dose-response curve (DRC) of rats in the explicitly paired condition with respect to the DRC of rats in the explicitly unpaired condition. Analgesia was assessed with the tail-flick and hot-plate devices. In the tail-flick assessment, associative tolerance was evident in the 72-hr and the 6-hr IDI conditions only. In the hot-plate assessment, associative tolerance was present in the 72-hr IDI condition only. The findings suggest that contextual tolerance to nicotine's analgesic effects are positively related to IDI length and are more readily demonstrated with the tail-flick method than with the hot-plate method. Overall, the results supported the thesis that nicotine tolerances that develop to different IDIs are qualitatively different and may be mediated by different psychological and physiological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)