Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: Implications for drug addiction

It has been suggested that some of the addictive potential of psychostimulant drugs of abuse such as amphetamine may result from their ability to enhance memory for drug-related experiences through actions on memory consolidation. This experiment examined whether amphetamine can specifically enhance consolidation of memory for a Pavlovian association between a neutral conditioned stimulus (CS-a light) and a rewarding unconditioned stimulus (US-food), as Pavlovian conditioning of this sort plays a major role in drug addiction. Male Long-Evans rats were given six training sessions consisting of 8 CS presentations followed by delivery of the food into a recessed food cup. After the 1st, 3rd, and 5th session, rats received subcutaneous injections of amphetamine (1.0 or 2.0 mg/kg) or saline vehicle immediately following training. Conditioned responding was assessed using the percentage of time rats spent in the food cup during the CS relative to a pre-CS baseline period. Both amphetamine-treated groups showed significantly more selective conditioned responding than saline controls. In a control experiment, there were no differences among groups given saline, 1.0 or 2.0 mg/kg amphetamine 2 h post-training, suggesting that immediate post-training amphetamine enhanced performance specifically through actions on memory consolidation rather than through non-mnemonic processes. This procedure modeled Pavlovian learning involved in drug addiction, in which the emotional valence of a drug reward is transferred to neutral drug-predictive stimuli such as drug paraphernalia. These data suggest that amphetamine may contribute to its addictive potential through actions specifically on memory consolidation.     

Pavlovian contingencies and resistance to change in a multiple schedule

According to theoretical accounts of behavioral momentum, the Pavlovian stimulus—reinforcer contingency determines resistance to change. To assess this prediction, 8 pigeons were exposed to an unsignaled delay-of-reinforcement schedule (a tandem variable-interval fixed-time schedule), a signaled delay-of-reinforcement schedule (a chain variable-interval fixed-time schedule), and an immediate, zero-delay schedule of reinforcement in a three-component multiple schedule. The unsignaled delay and signaled delay schedules employed equal fixed-time delays, with the only difference being a stimulus change in the signaled delay schedule. Overall rates of reinforcement were equated for the three schedules. The Pavlovian contingency was identical for the unsignaled and immediate schedules, and response—reinforcer contiguity was degraded for the unsignaled schedule. Results from two disruption procedures (prefeeding subjects prior to experimental sessions and adding a variable-time schedule to timeout periods separating baseline components) demonstrated that response—reinforcer contiguity does play a role in determining resistance to change. The results from the extinction manipulation were not as clear. Responding in the unsignaled delay component was consistently less resistant to change than was responding in both the immediate and presignaled segments of the signaled delay components, contrary to the view that Pavlovian contingencies determine resistance to change. Probe tests further supported the resistance-to-change results, indicating consistency between resistance to change and preference, both of which are putative measures of response strength.     

The development of an attentional bias for angry faces following Pavlovian fear conditioning

Although it is well documented that fear responses develop following aversive Pavlovian conditioning, it is unclear whether fear learning also manifests in the form of attentional biases for fear-related stimuli. Boschen, Parker, and Neumann (Boschen, M. J., Parker, I., & Neumann, D. L. (2007). Changes in implicit associations do not occur simultaneously to Pavlovian conditioning of physiological anxiety responses. Journal of Anxiety Disorders, 21, 788-803.) showed that despite the acquisition of differential skin conductance conditioned responses to angry faces paired (CS+) and unpaired (CS−) with an aversive shock, development of implicit associations was not subsequently observed on the Implicit Association Test. In the present study, participants (N = 76) were assigned either to a Shock or NoShock group and completed a similar aversive Pavlovian conditioning procedure with angry face CS+ and CS− stimuli. Participants next completed a visual probe task in which the angry face CS+ and CS− stimuli were paired with angry face control stimuli and neutral faces. Results confirmed that differential fear conditioning was observed in the Shock group but not in the NoShock group, and that the Shock group subsequently showed a selective attentional bias for the angry face CS+ compared with the CS− and control stimuli during the visual probe task. The findings confirm the interplay between learning-based mechanisms and cognitive processes, such as attentional biases, in models of fear acquisition and have implications for treatment of the anxiety disorders.     

Past experience influences the processing of stimulus compounds in human Pavlovian conditioning

In two human skin conductance conditioning experiments we investigated whether processing of stimulus compounds can be influenced by past experience. Participants were either pre-trained with a discrimination problem that could be solved elementally (A+, B−, AB+, C− in Experiment 1 and A+, AB+, C−, CB− in Experiment 2) or one that required a configural solution (AB+, BC−, CD+, DA− in Experiment 1 and A−, AB+, C+, CB− in Experiment 2). After pre-training, participants were shown an EX+, FX− discrimination. Subsequently, responding to individual components (E and F) was tested. After elemental pre-training, participants showed larger responses to the component from the previously reinforced compound (E) than to the component from the nonreinforced compound (F) whereas no such difference was found after configural pre-training. This means that the kind of pre-training influenced whether the later discrimination problem was processed elementally or configurally. The results indicate that organisms can flexibly process stimulus compounds in different ways.     

Contextual influences on resistance to disruption in children with intellectual disabilities

Training context can influence resistance to disruption under differing reinforcement schedules. With nonhumans, when relatively lean and rich reinforcement schedules are experienced in the context of a multiple schedule, greater resistance is found in the rich than the lean component, as described by behavioral momentum theory. By contrast, when the schedules are experienced in separated blocks of sessions (i.e., as single schedules), resistance is not consistently greater in either component. In the current study, two groups of 6 children with intellectual disabilities responded to stimuli presented in relatively lean or rich components. For both, reinforcers were delivered according to the same variable-interval reinforcement schedule; additionally, the rich component included the delivery of response-independent reinforcers. The Within group was trained on a multiple schedule in which lean and rich components alternated regularly within sessions; the Blocked group was trained on two single schedules in which sessions with either the lean or rich schedule were conducted in successive blocks. Disruption tests presented a concurrently available alternative stimulus disrupter signaling the availability of tangible reinforcers. All 6 Within participants showed greater resistance to disruption in the rich component, consistent with behavioral momentum theory. By contrast, there was no consistent or significant difference in resistance for Blocked participants. This finding is potentially relevant to the development of interventions in applied settings, where such interventions often approximate single schedules and include response-independent reinforcers.     

Behavioral momentum and resistance to extinction across repeated extinction tests

The present experiments assessed whether resistance to extinction of pigeons' key pecking decreased across repeated extinction tests. An additional impetus for this research was to determine how the quantitative framework provided by behavioral momentum theory might be used to describe any such changes across tests. Pigeons pecked keys in two‐component multiple schedules (one component associated with a higher reinforcer rate and the other with a lower rate) in which baseline and extinction conditions alternated. In Experiment 1, baseline and extinction conditions alternated every session, and, in Experiment 2, these conditions lasted for 10 and 7 sessions, respectively. Resistance to extinction decreased across successive extinction conditions in both experiments. Fits of the behavioral‐momentum based model of extinction to the data returned uncertain results in Experiment 1 but implicated both generalization decrement and response–reinforcer contingency termination as the possible mechanisms responsible for behavior change in Experiment 2. Thus, these data suggest that experimental manipulations that affect discrimination of changes in reinforcement contingencies may influence resistance to extinction by modulating the disruptive impacts of removing reinforcers from the experimental context and of suspending response–reinforcer contingencies.     

Differential contributions of dorsal vs. ventral hippocampus to auditory trace fear conditioning

The effect of excitotoxic lesions of dorsal vs. ventral hippocampus on the acquisition and expression of auditory trace fear conditioning was examined in two studies. In Experiment 1, animals received excitotoxic lesions of either the dorsal or ventral hippocampus or sham surgeries one week prior to conditioning, and were tested 24 h later. In Experiment 2, animals received excitotoxic lesions of either the dorsal or ventral hippocampus or sham surgeries 24 h after training, and were tested one week after surgery. Both pre- and post-training lesions of ventral hippocampus impaired the acquisition and expression, respectively, of auditory trace fear conditioning. Pre-training lesions of dorsal hippocampus had no effect on the acquisition of trace fear conditioning, while post-training lesions of dorsal hippocampus dramatically impaired expression during subsequent testing. Although in some cases animals with lesions of ventral hippocampus exhibited locomotor hyperactivity, it is unlikely that the pattern of observed deficits can be attributed to this effect. Collectively these data suggest that the dorsal and ventral hippocampus may contribute differentially to the mnemonic processes underlying fear trace conditioning.     

Examining the sex- and circadian dependency of a learning phenotype in mice with glycine transporter 1 deletion in two Pavlovian conditioning paradigms

Behavioural characterisation of transgenic mice has been instrumental in search of therapeutic targets for the modulation of cognitive function. However, little effort has been devoted to phenotypic characterisation across environmental conditions and genomic differences such as sex and strain, which is essential to translational research. The present study is an effort in this direction. It scrutinised the stability and robustness of the phenotype of enhanced Pavlovian conditioning reported in mice with forebrain neuronal deletion of glycine transporter 1 by evaluating the possible presence of sex and circadian dependency, and its consistency across aversive and appetitive conditioning paradigms. The Pavlovian phenotype was essentially unaffected by the time of testing between the two circadian phases, but it was modified by sex in both conditioning paradigms. We observed that the effect size of the phenotype was strongest in female mice tested during the dark phase in the aversive paradigm. Critically, the presence of the phenotype in female mutants was accompanied by an increase in resistance to extinction. Similarly, enhanced conditioned responding once again emerged solely in female mutants in the appetitive conditioning experiment, which was again associated with an increased resistance to extinction across days, but male mutants exhibited an opposite trend towards facilitation of extinction. The present study has thus added hitherto unknown qualifications and specifications of a previously reported memory enhancing phenotype in this mouse line by identifying the determinants of the magnitude and direction of the expressed phenotype. This in-depth comparative approach is of value to the interpretation of behavioural findings in general.     

Signaled alternative reinforcement and the persistence of operant behavior

Differential reinforcement of alternative behavior (DRA) is a treatment designed to eliminate problem behavior by reinforcing an alternative behavior at a higher rate. Availability of alternative reinforcement may be signaled, as with Functional Communication Training, or unsignaled. Whether or not alternative reinforcement is signaled could influence both the rate and persistence of problem behavior. The present study investigated whether signaling the availability of alternative reinforcement affects the rate and persistence of a concurrently available target response with pigeons. Three components of a multiple concurrent schedule arranged equal reinforcement rates for target responding. Two of the components also arranged equal reinforcement rates for an alternative response. In one DRA component, a discrete stimulus signaled the availability of response‐contingent alternative reinforcement by changing the keylight color upon reinforcement availability. In the other DRA component, availability of alternative reinforcement was not signaled. Target responding was most persistent in the unsignaled DRA component when disrupted by satiation, free food presented between components, and extinction, relative to the signaled DRA and control components. These findings suggest the discrete stimulus functionally separated the availability of alternative reinforcement from the discriminative stimuli governing target responding. These findings provide a novel avenue to explore in translational research assessing whether signaling the availability of alternative reinforcement with DRA treatments reduces the persistence of problem behavior.     

The resistance of renewal to instructions that devalue the role of contextual cues in a conditioned suppression task with humans

The renewal of extinguished conditioned behaviour appears to reflect context-dependent learning. The present research used a conditioned suppression task with humans to examine whether instructions concerning the context could influence renewal. Pairings of a conditional stimulus (CS) and unconditional stimulus (US) were made in one context, followed by extinction trials of CS alone in a second context, and test trials of CS alone upon return to the original learning context. Four experiments tested whether the renewal of conditioned suppression observed during test would be attenuated if participants were instructed that the context changes were irrelevant to the predictive relationship between the CS and US. Using a differential conditioning design, no attenuation was found when the instructions were given prior to conditioning (Experiment 1) or immediately prior to the test trials (Experiment 2). The latter result was replicated with a single-cue conditioning design and further controls for exposure to the extinction contexts (Experiment 3). The collection of on-line ratings about the relationship between the contextual changes and the predictive nature of the CS indicated that participants did attend to and believe the instructions (Experiment 4). The results point to the resistance of renewal to explicit instructions that attempt to devalue the role of the contextual cues.     

I. V. Zavadskii and the beginnings of behavioral pharmacology: an historical note and translation.

I. V. Zavadskii, who worked in Pavlov's laboratory between 1907 and 1909, performed a study that has many of the characteristics of modern behavioral pharmacology. He studied the effects of alcohol, morphine, cocaine and caffeine on the conditioned salivary reflex. A translation of his paper and some brief comments on his life are presented.     

The effects of constant versus varied reinforcers on preference and resistance to change

Previous research has demonstrated that factors such as reinforcer frequency, amount, and delay have similar effects on resistance to change and preference. In the present study, 4 boys with autism made choices between a constant reinforcer (one that was the same food item every trial) and a varied food reinforcer (one that varied randomly between three possible food items). For all 4 boys, varied reinforcers were preferred over constant reinforcers, and they maintained higher response rates than constant reinforcers. In addition, when a distraction (a video clip) was introduced, responding maintained by varied reinforcers was more resistant to distraction than responding maintained by constant reinforcers. Thus, the present experiment extended the generality of the relation between preference and resistance to change to variation in reinforcer quality.     

Rate of conditioned reinforcement affects observing rate but not resistance to change

The effects of rate of conditioned reinforcement on the resistance to change of operant behavior have not been examined. In addition, the effects of rate of conditioned reinforcement on the rate of observing have not been adequately examined. In two experiments, a multiple schedule of observing-response procedures was used to examine the effects of rate of conditioned reinforcement on observing rates and resistance to change. In a rich component, observing responses produced a higher frequency of stimuli correlated with alternating periods of random-interval schedule primary reinforcement or extinction. In a lean component, observing responses produced similar schedule-correlated stimuli but at a lower frequency. The rate of primary reinforcement in both components was the same. In Experiment 1, a 4:1 ratio of stimulus production was arranged by the rich and lean components. In Experiment 2, the ratio of stimulus production rates was increased to 6:1. In both experiments, observing rates were higher in the rich component than in the lean component. Disruptions in observing produced by presession feeding, extinction of observing responses, and response-independent food deliveries during intercomponent intervals usually were similar in the rich and lean components. When differences in resistance to change did occur, observing tended to be more resistant to change in the lean component. If resistance to change is accepted as a more appropriate measure of response strength than absolute response rates, then the present results provide no evidence that higher rates of stimuli generally considered to function as conditioned reinforcers engender greater response strength.     

Assessing the role of alternative response rates and reinforcer rates in resistance to extinction of target responding when combining stimuli

Studies of behavioral momentum reveal that reinforcing an alternative response in the presence of a target response reduces the rate of target responding but increases its persistence, relative to training the target response on its own. Because of the parallels between these studies and differential‐reinforcement techniques to reduce problem behavior in clinical settings, alternative techniques to reduce problem behavior without enhancing its persistence are being explored. One potential solution is to train an alternative response in a separate stimulus context from problem behavior before combining the alternative stimulus with the target stimulus. The present study assessed how differences in reinforcement contingencies and rate for alternative responding influenced resistance to extinction of target responding when combining alternative and target stimuli in pigeons. Across three experiments, alternative stimuli signaling a response–reinforcer dependency and greater reinforcer rates more effectively decreased the persistence of target responding when combining alternative and target stimuli within the same extinction tests, but not when compared across separate extinction tests. Overall, these findings reveal that differences in competition between alternative and target responding produced by contingencies of alternative reinforcement could influence the effectiveness of treating problem behavior through combining stimulus contexts.     

Evaluation of resistance to change under different disrupter conditions in children with autism and severe intellectual disability

Translational research inspired by behavioral momentum theory in the area of developmental disabilities has shown effects in individuals over a range of functioning levels. In the current study, behavioral momentum was assessed in 6 children diagnosed with autism and severe intellectual disability. In a repeated measures design, participants were exposed to relatively rich versus lean reinforcement contingencies in a multiple schedule with food reinforcers. This was followed by exposure to each of four disrupting conditions: prefeeding, presentation of a concurrent alternative stimulus, presentation of a movie, and the presence of a researcher dispensing response-independent reinforcers on a variable-time schedule. Consistently greater resistance to disruption in the component with the richer schedule occurred with the alternative stimulus disrupter but not with the other disrupters. These results suggest parameters that may be more (or less) effective if behavioral momentum inspired techniques are to be exploited in therapeutic environments.     

Preference and resistance to change with constant- and variable-duration terminal links: independence of reinforcement rate and magnitude

Pigeons responded in a three-component multiple concurrent-chains procedure in which the variable-interval reinforcement schedules were the same across components but magnitudes differed across components. The terminal links were arranged either as a variable delay followed by presentation of a reinforcer ("variable duration") or as a fixed period of access to the schedule during which a variable number of reinforcers could be earned ("constant duration"). Relative reinforcement rate was varied parametrically across both types of conditions. After baseline training in each condition, resistance to change of terminal-link responding was assessed by delivering food during the initial links according to a variable-time schedule. Both preference and resistance to change were more sensitive to reinforcement-rate differences in the constant-duration conditions. Sensitivities of preference and resistance to change to relative reinforcement rate did not change depending on relative reinforcement magnitude. Taken together, these results confirm and extend those of prior studies, and suggest that reinforcement rate and magnitude combine additively to determine preference and resistance to change. A single structural relation linking preference and resistance to change describes all the data from this and several related studies.