Effects of extinction context and retrieval cues on alcohol cue reactivity among nonalcoholic drinkers.

Pavlovian conditioning models have influenced the development of cue exposure treatments for drug abuse. However, poor maintenance of extinction performance (renewal) after treatment is a common problem. A treatment-analogue experiment tested the role of context in renewal, as well as a potential strategy for reducing renewal. Seventy-eight social drinkers completed extinction trials to reduce saliva and urge reactivity to alcohol cues and were randomly assigned to a renewal test in either the same context as extinction, a different context, or the different context containing a cue from the extinction context (E-cue). As predicted, the different context produced greater renewal than the same context and renewal was attenuated when the E-cue was present. These results offer preliminary evidence for the context dependence of extinction to alcohol cues and for the use of an extinction cue to improve the generalizability of exposure therapies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of extinction context and retrieval cues on renewal of alcohol-cue reactivity among alcohol-dependent outpatients.

Pavlovian conditioning models have led to cue-exposure treatments for drug abuse. However, conditioned responding to drug stimuli can return (be renewed) following treatment. Animal research and a previous study of social drinkers indicated that extinction is highly context dependent but that renewal could be reduced by the inclusion of a cue from the extinction context. This study extends this research to a clinical sample. Alcohol-dependent outpatients (N = 143) completed an extinction trial to reduce craving and salivation responses to alcohol cues. They were then randomized to renewal tests in either the same context as extinction, a different context, the different context containing an extinction cue, or the different context with cue plus a manipulation to increase the salience of the cue. Contrary to predictions, the different context did not produce the expected renewal effect. Although the generalization of extinction effects beyond the cue-exposure context is a positive clinical finding, it is inconsistent with basic research findings on the context dependence of extinction. Possible explanations for this inconsistency are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A retrieval cue for extinction attenuates response recovery (renewal) caused by a return to the conditioning context.

When conditioning and extinction are conducted in different contexts, a return to the conditioning context causes a renewal of conditioned responding. The results of 4 experiments with rats in an appetitive conditioning preparation suggest that renewal results from a failure to retrieve extinction outside the extinction context. Presentation of a cue from extinction during renewal testing attenuated the renewal effect; attenuation depended on the cue's correlation with extinction. On its own, the cue did not elicit responding, suggesting it was not a conditioned excitor; it also failed tests for conditioned inhibition. The authors propose that it worked by retrieving a memory of extinction. The findings parallel previous results with spontaneous recovery and are thus consistent with the view that renewal and spontaneous recovery result from a common mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Environments as cues to smoke: Implications for human extinction-based research and treatment.

Animal research has shown that the environments, or contexts, in which drug use occurs can play a key role in how animals respond to drug-related cues. Less is known about the role of environmental contexts in human drug-dependence research. Traditionally, cue-based studies and treatments focus on conditioned cues most proximal to drug administration (e.g., lit cigarettes, pictorial stimuli of drug paraphernalia). However, there is reason to believe that more distal cues, such as the environments in which drugs were previously used, might similarly gain associative control over human responding. This article describes a body of systematic research aimed at identifying and studying the impact of environmental contexts on smokers' cue reactivity in the laboratory. Overall, results of this program of research demonstrate that exposure to environments associated with smoking, but completely devoid of proximal smoking cues, can function as conditioned stimuli capable of evoking strong subjective responding from abstinent smokers. Furthermore, more robust reactivity can be achieved if environmental context cues are personalized using novel techniques described in this article. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Backward conditioning: Mediation by the context.

The information acquired in backward conditioning (i.e., outcome→cue) was assessed in 3 Pavlovian lick-suppression experiments with water-deprived rats as subjects. Experiment 1 confirmed previous research that few outcome→cue pairings made the cue into a conditioned excitor and additionally showed that massive posttraining extinction of the training context attenuated a backward-trained cue's excitatory value. Experiment 2 found that many outcome→cue pairings made the cue into a conditioned inhibitor and that the same context manipulation attenuated this inhibitory value. Experiment 3 confirmed the observations of Experiments 1 and 2 and demonstrated that these effects of context extinction were specific to backward-trained cues conditioned in the extinguished context. These results are interpreted in terms of cue→context and context→outcome associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ethanol on encoding, consolidation, and expression of extinction following contextual fear conditioning.

Studies of contextual fear conditioning have found that ethanol administered prior to a conditioning session impairs the conditioned freezing response during a test session the next day. The present experiments examined the effects of ethanol on extinction, the loss of conditioned responding that occurs as the animal learns that a previously conditioned context no longer signals shock. Ethanol (1.5 g/kg) administered prior to single (Experiment 1) or multiple (Experiment 2) extinction sessions impaired extinction. Ethanol administered prior to a test session disrupted the expression of freezing after extinction (Experiments 3-5). There was some evidence that ethanol served as an internal stimulus signaling the operation of conditioning or extinction contingencies (Experiments 4-5). In Experiment 6, postsession injections of 1.5 g/kg ethanol had no effect on extinction with brief (3 min) or long (24 min) exposures to the context, but injections of 3 g/kg after long exposures impaired extinction. Together, these results indicate that ethanol affects extinction by acting on multiple learning and performance processes, including attention, memory encoding, and memory expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual control of conditioned responding in rats with dorsal hippocampal lesions.

The control exerted by contextual cues over classically conditioned responding was assessed for rats with electrolytic lesions of the dorsal hippocampus and sham-operated controls. In 3 experiments the rats received initial training with 2 reinforced cues, each presented in its own distinctive context, followed by a nonreinforced test in which the cues were presented in the other context. Both control and operated subjects showed context specificity, as evidenced by less vigorous responding to these cues than to cues presented on test in their original contexts. The groups did not differ in their ability to learn an explicit discrimination in which a given cue was reinforced in one context and nonreinforced in a different context (although the groups did differ on a simple autoshaping task). It is concluded that a special role for the hippocampus in the contextual control of conditioned responding still remains to be demonstrated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Craving and physiological reactivity to trauma and alcohol cues in posttraumatic stress disorder and alcohol dependence.

The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) has been firmly established. Although laboratory studies have examined self-reported craving in response to trauma and alcohol cues, no studies have reported on alcohol-related physiological responding in response to trauma cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol-related responding (e.g., salivation, craving) in individuals with PTSD and AD (n = 40). Participants displayed reactivity to both trauma and alcohol cues when compared to neutral cues, including increased self-reported craving and distress, as well as greater salivation. These findings suggest that through repeated pairings of trauma memories and alcohol consumption, salivation may become classically conditioned to trauma cues. Moreover, the fact that the trauma-alcohol cue combination elicited greater alcohol craving, salivary responding, distress, and arousal than either the trauma-neutral or neutral-alcohol cue combinations suggests that effects of the trauma and alcohol cues were additive in nature. Evidence that AD individuals with PTSD report increased alcohol craving and display greater salivation in response to trauma memories, supplements prior research indicating that PTSD-related negative emotion and trauma-related alcohol craving may play an important role in the maintenance of AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

mGluR5 positive allosteric modulation enhances extinction learning following cocaine self-administration.

Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study, the authors investigated the effects of the Type-5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in rats with a history of intravenous cocaine self-administration. To assess its effects on acquisition and consolidation of extinction learning, CDPPB (60 mg/kg) or vehicle was administered either 20 min prior to, or immediately following, each of 10 extinction sessions, respectively. When administered prior to each extinction session, CDPPB produced a significant reduction in the number of active lever presses on all 10 days of extinction training as compared to vehicle-treated animals. When administered following each extinction session, a significant reduction in the number of active lever presses was observed on the 2nd through 10th day of extinction. Both treatment regimens also reduced the number of extinction-training sessions required to meet extinction criteria. Pre- or postextinction-training administration of CDPPB did not alter responding on the inactive lever and had no effects on open field locomotor activity. These data indicate that positive allosteric modulation of mGluR5 receptors facilitates the acquisition and consolidation of extinction learning following cocaine self-administration and may provide a novel pharmacological approach to enhancing extinction learning when combined with cue exposure therapy for the treatment of cocaine addiction. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The role of the rat hippocampal system in several effects of context in extinction.

The effect of fornix lesions on some effects of manipulating the context on performance in extinction were studied. In renewal, subjects' responding to an extinguished CS recovered when the CS was presented in the context in which it had been conditioned after extinction in a different context. In reinstatement, it recovered when the CS was tested after independent presentation of the unconditioned stimulus (UCS; an effect mediated by contextual conditioning.) In spontaneous recovery, it recovered after the passage of time, that is, when the CS was tested in a new temporal context. In the conditioned suppression method, fornix lesions had no effect on conditioning, extinction, renewal, or spontaneous recovery; however, they abolished the reinstatement effect. The results suggest that the hippocampal system may be important in the formation of context–UCS associations, but not in other types of learning about the context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus competition between a discrete cue and a training context: Cue competition does not result from the division of a limited resource.

Several associative learning theories explain cue competition as resulting from the division of a limited resource among competing cues. This leads to an assumption that behavioral control by 2 cues competing with each other should always reflect a tradeoff, resulting in apparent conservation of total reinforcer value across all competing cues. This assumption was tested in 3 conditioned lick suppression experiments with rats, investigating the effects of changing the conditioned stimulus (CS) duration (Experiment 1), administering pretraining exposures to the CS (Experiment 2), and presenting nonreinforced CSs during the intertrial interval (Experiment 3) on Pavlovian conditioned responding to both the CS and the conditioning context. Fear conditioned to the context and to the CS decreased when the CS was of longer duration, massively preexposed before being paired with the reinforcer, or presented alone during the intertrial interval. These observations are problematic for the theories that explain cue competition as the division of a limited resource and suggest that the total reinforcer value across competing cues is not always fixed for a given reinforcer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The hide-and-seek of retrospective revaluation: Recovery from blocking is context dependent in human causal learning.

In a typical blocking procedure, pairings of a compound consisting of 2 stimuli, A and X, with the outcome are preceded by pairings of only A with the outcome (i.e., A+ then AX+). This procedure is known to diminish responding to the target cue (X) relative to a control group that does not receive the preceding training with blocking cue A. We report 2 experiments that investigated the effect of extinguishing a blocking cue on responding to the target cue in a human causal learning paradigm (i.e., A+ and AX+ training followed by A– training). The results indicate that extinguishing a blocking cue increases conditioned responding to the target cue. Moreover, this increase appears to be context dependent, such that increased responding to the target is limited to the context in which extinction of the blocking cue took place. We discuss these findings in the light of associative and propositional learning theories. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Two roles of the context in Pavlovian fear conditioning.

At both empirical and theoretical levels, multiple functional roles of contextual information upon memory performance have been proposed without a clear dissociation of these roles. Some theories have assumed that contexts are functionally similar to cues, whereas other views emphasize the retrieval facilitating properties of contextual information. In Experiment 1, we observed that one critical parameter, the spacing of trials, could determine whether the context would function as a conditioned stimulus or as a retrieval cue for memories trained in different phases. Experiments 2 and 3 doubly dissociated these functions by selectively disrupting one role but not the other, and vice versa. Overall, these observations identify one determinant of different functions of contextual information and pose a major challenge to theories of learning that assume exclusively one or the other function of the context. Moreover, these data emphasize the importance of parametric variations on behavioral control, which has critical implications for studies designed to understand the role of the hippocampus in processing of contextual attributes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context switch effects on acquisition and extinction in human predictive learning.

Four experiments tested context switch effects on acquisition and extinction in human predictive learning. A context switch impaired probability judgments about a cue-outcome relationship when the cue was trained in a context in which a different cue underwent extinction. The context switch also impaired judgments about a cue trained in a context different from the extinction context, whenever this training was concurrent with extinction of another cue. After extinction, new cue-outcome relationships learned, even in a different task, became context specific. Moreover, renewal was consistently observed. It is suggested that context switch effects result from a process by which ambiguity leads participants to attend to the contexts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative electrophysiologic findings between responders and nonresponders to class III antiarrhythmic drugs among patients with ventricular tachyarrhythmia

Rabbits received conditional discrimination training using contextual stimuli to set the occasion for stimulus pairings during eyelid conditioning. Specifically, animals were exposed to either the presence or the absence of an oscillating chamber light throughout the intertrial interval (50 +/- 10 s). For half the animals, this light signaled paired presentations of a discrete tone conditioned stimulus (CS) and air puff unconditioned stimulus (US) while darkness signaled presentations of only the tone CS. The remaining animals experienced the opposite contextual relationship to the conditioning stimuli. These trial types occurred pseudo-randomly across a session, with all transitions between contextual settings (i.e., light or dark) taking place immediately at the CS-US offset. Under these conditions, animals successfully utilized the contextual stimuli as conditional cues for differential responding to the shared CS. Moreover, both light and dark were equally effective as discriminative stimuli. A subset of animals received further training in which the contextual contingency was removed by restricting all conditioning to the CS-alone context. Without the contingency in place, subsequent CS presentations (paired and CS-alone) evoked equivalent conditioned responding across three sessions of training. Following the reinstatement of the contextual contingencies, discriminatory responding was immediately observed and returned to previous levels within three sessions. Finally, animals appeared to use the static representation of the conditional cue, rather than the phasic transition between cues, for discriminatory responding. These findings are discussed in terms of current neurobiological models of eyelid conditioning.     

A retrieval cue for extinction attenuates spontaneous recovery.

Four experiments with rats in an appetitive conditioned magazine entry preparation examined spontaneous recovery after extinction. Spontaneous recovery was obtained 6 days but not 5 hrs following extinction; recovery depended on the passage of time but not on the removal of a cue that was featured in extinction or on the reintroduction of early-session cues. A cue featured in extinction attenuated recovery when presented on the test. The attenuation effect depended on the cue's correlation with extinction; a cue featured in conditioning did not attenuate recovery. The extinction cue did not evoke responding on its own, suggesting that it was not a conditioned excitor. Retardation tests and a summation test did not reveal that it was a conditioned inhibitor. The cue might work by retrieving a memory of extinction. Spontaneous recovery thus occurs because the S fails to retrieve an extinction memory. Other accounts of spontaneous recovery are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experimental renewal in human participants.

Two experiments with human participants are presented that differentiate renewal from other behavioral effects that can produce a response after extinction. Participants played a video game and learned to suppress their behavior when sensor stimuli predicted an attack. Contexts (A, B, & C) were provided by fictitious galaxies where the game play took place. In Experiment 1, participants who received conditioning in A, extinction in B, and testing in A showed some context specificity of conditioning during extinction and a recovery of suppression on test. Experiment 2 demonstrated recovery of extinguished responding when participants were conditioned in A, extinguished in B, and tested in C, a third, neutral context. The experiment also demonstrated that the context of extinction did not control performance by becoming inhibitory. Results are discussed in terms of mechanisms that can produce a response recovery after extinction. The experiments demonstrated a renewal effect: a response recovery that was not attributable to the contexts acting as simple conditioned stimuli and is the first work with human participants to conclusively do so. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exposure therapy renewed.

Recurrence of posttraumatic stress disorder (PTSD) symptoms after treatment has been a long-standing problem. Recent theories of PTSD suggest that different types of processing (i.e., sensory vs. conceptual) may contribute to the return of symptoms. Patients who process their experience primarily via sensory cues (i.e., focusing on the specific environmental cues present at the time of the trauma) are more likely to develop the automatic, physiologically based symptoms of PTSD, which are often the most debilitating. Exposure therapy, based on conditioning principles related to extinction, may be a first-line course of treatment. Contemporary learning theory suggests ways to change exposure treatment to limit the reappearance of symptoms. This research suggests that lengthy and numerous exposure sessions, the use of conditioned inhibitors, and creating a maximal excitatory exposure context can yield efficacious treatment and minimize the likelihood of symptom renewal. Moreover, means for constructing the optimal exposure context are discussed via the use of free association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reactivity of alcoholics and nonalcoholics to drinking cues.

An interest in reducing relapse among alcoholics has led to a consideration of stimulus control factors in drinking. Research suggests that through classical conditioning alcoholics may develop reactions to cues previously associated with drinking and that these reactions might be an important determinant of relapse. Although this model indicates the potential for cue exposure treatment methods to alter conditioned reactions, data on reactivity to alcohol cues by alcoholics and nonalcoholics are scarce. Two studies are presented that address this issue and provide evidence for the validity of salivation as a measure of cue reactivity. Alcoholics and nonalcoholics were presented with the sight and smell of their preferred brand of alcohol and a control beverage. Self-report, behavioral, and psychophysiological data were collected. Alcoholics salivated more than nonalcoholics to alcohol cues and more to alcohol than to the control beverage. Alcoholics salivated differentially to cues, whereas nonalcoholics did not. Patterns of reactivity were consistent with a conditioning model. Both groups reported greater urges to drink alcohol in the presence of alcohol, but neither group reported more thoughts about alcohol in the presence of alcohol as compared with the control beverage. Implications of salivary reactivity for theory and treatment are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol expectancies and reactivity to alcohol-related and affective cues.

Recent conceptualizations of alcohol expectancies relate cognitive schemas to their neurobiological underpinnings; cue reactivity paradigms lend themselves well to testing this broadened conceptual framework. In the present study, we examined the relationship between self-reported alcohol expectancies and responses to alcohol-related and affective picture cues among fifty-five young adults. In addition to traditional subjective and psychophysiological indices of cue reactivity, the startle eyeblink reflex was obtained during picture cue presentations to address both attention-arousal (early probes) and affective-motivational (late probes) aspects of cue processing. Analyses indicated that participants reporting greater positive, arousing, and social alcohol expectancies rated alcohol cues as more pleasant, arousing, and craving-inducing. In addition, participants displayed inhibited startle reactivity to late alcohol cue probes, indicative of an appetitive reaction. Finally, startle responding to early probes indicated that participants with greater alcohol expectancies displayed blunted attention to negative affect cues. Findings are discussed in terms of the utility of the startle reflex and cue reactivity paradigms for clarifying the relationship between alcohol expectancies and motivated attention to salient cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)