Amphetamine exposure enhances habit formation

Performance of instrumental actions in rats is initially sensitive to postconditioning changes in reward value, but after more extended training, behavior comes to be controlled by stimulus–response (S-R) habits that are no longer goal directed. To examine whether sensitization of dopaminergic systems leads to a more rapid transition from action–outcome processes to S-R habits, we examined performance of amphetamine-sensitized rats in an instrumental devaluation task. Animals were either sensitized (7 d, 2 mg/kg/d) before training (experiment 1) or sensitized between training and testing (experiment 2). Rats were trained to press a lever for a reward (three sessions) and were then given a test of goal sensitivity by devaluation of the instrumental outcome before testing in extinction. Control animals showed selective sensitivity to devaluation of the instrumental outcome. However, amphetamine sensitization administered before training caused the animals’ responding to persist despite the changed value of the reinforcer. This deficit resulted from an inability to use representations of the outcome to guide behavior, because a reacquisition test confirmed that all of the animals had acquired an aversion to the reinforcer. In experiment 2, post-training sensitization did not disrupt normal goal-directed behavior. These findings indicate that amphetamine sensitization leads to a rapid progression from goal-directed to habit-based responding but does not affect the performance of established goal-directed actions

Prefrontal cortex lesions disrupt the contextual control of response conflict

The prefrontal cortex has been implicated in multiple forms of goal-directed behavior. Rats with pretraining lesions to the prefrontal cortex (PFC) or specific lesions to the anterior cingulate cortex (ACC) were trained and tested on a novel behavioral procedure measuring aspects of cue and response competition typical of tests of prefrontal function in humans. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two discriminably different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in both contexts, in extinction. These compounds were formed in such way that the individual elements had dictated either the same (congruent trials) or different (incongruent trials) responses during training. Sham-operated rats used the contextual cues to disambiguate the conflicting response information provided by incongruent stimulus compounds. ACC lesions impaired the contextual control of instrumental responding during incongruent cues during only the initial period of cue presentation, whereas larger PFC lesions abolished incongruent cue performance completely. Neither biconditional discrimination acquisition, nor test performance during congruent stimulus compounds, were affected by the lesions. These findings are consistent with human and nonhuman primate studies, indicating a role for the PFC in the processes by which cues come to control behavior in the face of conflicting information and the ACC specifically in processes such as detection of response conflict. This procedure provides a good foundation for an improved understanding of the disruption to goal-directed behavior seen with frontal dysfunction in a number of neuropsychological disorders including schizophrenia

Lesions of the basolateral amygdala disrupt conditioning based on the retrieved representations of motivationally significant events

One recent perspective (Blundell et al., 2001; 2003; Killcross and Blundell, 2002; Balleine et al. 2003) on the function of the basolateral region of the amygdala (BLA) suggests that it plays an important role in the representation of the sensory features of motivationally significant events. This predicts that lesions of the BLA will not produce a decrement in performance in conditioning procedures based on the formation of associations between the sensory aspects of neutral events but will interfere with conditioning based on associations between neutral cues and motivationally significant events. This prediction is supported by the evidence that BLA lesions were without effect on a sensory preconditioning procedure (experiment 1A) that used neutral cues but that BLA lesions did significantly impair representation-mediated conditioning (experiment 1B) when the target cues were motivationally significant at the time of training. These results demonstrate that animals with lesions of the BLA can represent the sensory aspects of neutral events but not the sensory aspects of motivationally significant events

Lesions of the basolateral amygdala disrupt selective aspects of reinforcer representation in rats

The amygdala is known to play a role in learning about motivationally significant events. We investigated this role further by examining the effects of excitotoxic lesions of the basolateral amygdala on the ability of rats to use instrumental outcomes to direct responding (the differential outcomes effect) and on the ability of Pavlovian cues to modulate instrumental performance based on shared outcomes (reinforcer–selective Pavlovian-to-instrumental transfer). We found that basolateral amygdala (BLA) lesions did not affect the ability of rats to learn a basic instrumental conditional discrimination, but did disrupt the ability of differential outcomes to facilitate acquisition. In Pavlovian-to-instrumental transfer, BLA lesions did not disrupt the basic enhancement of instrumental performance but did abolish the reinforcer specificity of that enhancement. These results suggest that the BLA is involved in the representation of the sensory aspects of motivationally significant events

Inactivation of the infralimbic prefrontal cortex in rats reduces the influence of inappropriate habitual responding in a response-conflict task

Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. One discrimination was “over-trained” relative to the other, “under-trained,” discrimination in the ratio 3:1. At test, animals were presented with incongruent audiovisual stimulus compounds of the training stimuli in the under-trained context. The stimulus elements of these test compounds have previously dictated different lever press responses during training. Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding

Parallel incentive processing: an integrated view of amygdala function

The amygdala is a heterogeneous structure that has been implicated in a wide variety of functions, most notably in fear conditioning. From this research, an influential serial model of amygdala processes has emerged in which aversive learning is mediated by the amygdala basolateral nucleus whereas performance, in this case of various defensive reflexes, is mediated by the central nucleus. By contrast, recent evidence from appetitive conditioning studies suggests that the basolateral and central nuclei operate in parallel to mediate distinct incentive processes: the basolateral nucleus encodes emotional events with reference to their particular sensory-specific features, whereas the central nucleus encodes their more general motivational or affective significance. Given that there is little if any direct behavioral evidence for the serial model, we suggest that more attention should be given to the claims of the parallel view

Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006). To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (3 sessions). Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1a-1c) or in non-sensitized animals (Experiment 2). Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behaviour is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behaviour

Contextual Control of Choice Performance: Behavioral, Neurobiological, and Neurochemical Influences

An important aspect of decision making is the ability of responses to be controlled by different cues in different situations or contexts, especially when there is conflict between alternative responses or actions.Recently, a context-dependent biconditional task has been developed for rats that mimic some aspects of response conflict seen in human cognitive paradigms, such as the Stroop task. In this task, contextual cues are used to disambiguate conflicting response information provided by audiovisual compound stimuli. Here we review current findings that investigate some of the behavioral, neurobiological, and neurochemical mechanisms that underlie this use of contextual or task-setting information to resolve response conflict, and discuss future ways in which this research can be extended

Both motivational and training factors affect response conflict choice performance in rats

Rats were trained on two biconditional discrimination tasks, in two different contexts, and were rewarded with two different outcomes. At test, they received presentations of audiovisual compounds of these training stimuli, in extinction. These compounds were formed in such way that the individual elements had dictated either the same (congruent trials) or different (incongruent trials) responses during training, and each stimulus element had previously been rewarded with a different outcome. Previous research has shown that rats use the contextual cues to disambiguate the conflicting response information provided by incongruent stimulus compounds. Experiment 1 demonstrated that this contextual control was goal-directed in the sense that it depended on the current value of the outcome and Experiment 2 demonstrated that both the training history of the biconditional stimuli and motivational influences influenced the contextual control of responding on incongruent trials. These results are discussed in relation to current models of choice behaviour

Contextual control of biconditional task performance: Evidence for cue and response competition in rats

A novel paradigm is presented that was designed to mimic aspects of cue and response competition seen in humans in conflict procedures such as the Stroop task. Rats were trained simultaneously on two biconditional discrimination tasks, one auditory and one visual, in two different contexts: C1, in which A1:LP1 → R, A2:LP2 → R; and C2, in which V1:LP1 → R, V2:LP2 → R, where C1/C2 represent different training contexts (produced by different operant chambers), A1/A2 are different auditory cues, V1/V2 are different visual cues, LP1/LP2 are discrete operant responses, and R is reward. At test, rats received presentations of audiovisual compounds of these training stimuli in extinction. These compounds had dictated either the same (A1V1 or A2V2) or different (A1V2 or A2V1) responses during training: termed congruent and incongruent trials, respectively. Experiment 1 showed that following equal training on the two biconditional tasks, the contextual cues came to control responding to conflicting information provided by incongruent stimulus compounds such that animals responded according to the stimulus element previously trained in that test context. Experiment 2 demonstrated that differential training on the biconditional discriminations (with rats receiving training on the two discriminations in the ratio 31) resulted in greater interference from the overtrained task when animals were tested in the undertrained context. This finding is similar to the classic Stroop asymmetry seen in human performance whereby dominant word reading interferes with colour naming for incongruent colour–word compounds. Further analysis also revealed some evidence for a reverse Stroop effect in which the undertrained stimulus element interfered with performance on the overtrained task