Pavlovian-instrumental Transfer Test Research Articles

Obsessive-compulsive disorder is characterized by decreased Pavlovian influence on instrumental behavior.

Obsessive-compulsive disorder (OCD) is characterized by uncontrollable repetitive actions thought to rely on abnormalities within fundamental instrumental learning systems. We investigated cognitive and computational mechanisms underlying Pavlovian biases on instrumental behavior in both clinical OCD patients and healthy controls using a Pavlovian-Instrumental Transfer (PIT) task. PIT is typically evidenced by increased responding in the presence of a positive (previously rewarded) Pavlovian cue, and reduced responding in the presence of a negative cue. Thirty OCD patients and thirty-one healthy controls completed the Pavlovian Instrumental Transfer test, which included instrumental training, Pavlovian training for positive, negative and neutral cues, and a PIT phase in which participants performed the instrumental task in the presence of the Pavlovian cues. Modified Rescorla-Wagner models were fitted to trial-by-trial data of participants to estimate underlying computational mechanism and quantify individual differences during training and transfer stages. Bayesian hierarchical methods were used to estimate free parameters and compare the models. Behavioral and computational results indicated a weaker Pavlovian influence on instrumental behavior in OCD patients than in HC, especially for negative Pavlovian cues. Our results contrast with the increased PIT effects reported for another set of disorders characterized by compulsivity, substance use disorders, in which PIT is enhanced. A possible reason for the reduced PIT in OCD may be impairment in using the contextual information provided by the cues to appropriately adjust behavior, especially when inhibiting responding when a negative cue is present. This study provides deeper insight into our understanding of deficits in OCD from the perspective of Pavlovian influences on instrumental behavior and may have implications for OCD treatment modalities focused on reducing compulsive behaviors.

General Pavlovian-instrumental transfer tests reveal selective inhibition of the response type – whether Pavlovian or instrumental – performed during extinction

The present experiments examined whether extinction of a stimulus predicting food affects the ability of that stimulus to energize instrumental performance to obtain food. We first used a general Pavlovian instrumental transfer (PIT) paradigm in which rats were first given Pavlovian conditioning with a stimulus predicting one type of food outcome and were then trained to lever press for a different food outcome. We found that the Pavlovian stimulus enhanced performance of the lever press response and that this enhancement was preserved after extinction of that stimulus (Experiment 1) even when the context was manipulated to favor the expression of extinction (Experiment 2). Next, we assessed whether extinction influenced the excitatory effect of a stimulus when it was trained as a discriminative stimulus. Extinction of this stimulus alone had no effect on its ability to control instrumental performance; however, when extinguished with its associated lever press response, discriminative control was lost (Experiments 3 and 4). Finally, after instrumental and Pavlovian training, we extinguished a Pavlovian stimulus predicting one food outcome with a lever press response that delivered a different outcome. In a general PIT test, we found this extinction abolished the ability of the Pavlovian stimulus to elevate responding on a lever trained with a different outcome, revealing for the first time that extinction can abolish the general PIT effect. We conclude that extinction can produce an inhibitory association between the stimulus and the general response type, whether Pavlovian or instrumental, performed during the extinction training.

Inferring action-dependent outcome representations depends on anterior but not posterior medial orbitofrontal cortex.

Although studies examining orbitofrontal cortex (OFC) often treat it as though it were functionally homogeneous, recent evidence has questioned this assumption. Not only are the various subregions of OFC (lateral, ventral, and medial) hetereogeneous, but there is further evidence of heterogeneity within those subregions. For example, several studies in both humans and monkeys have revealed a functional subdivision along the anterior-posterior gradient of the medial OFC (mOFC). Given our previous findings suggesting that, in rats, the mOFC is responsible for inferring the likelihood of unobservable action outcomes (Bradfield, Dezfouli, van Holstein, Chieng, & Balleine, 2015), and given the anterior nature of the placements of our prior manipulations, we decided to assess whether the rat mOFC also differs in connection and function along its anteroposterior axis. We first used retrograde tracing to compare the density of efferents from mOFC to several structures known to contribute to goal-directed action: the mediodorsal thalamus, basolateral amygdala, posterior dorsomedial striatum, nucleus accumbens core and ventral tegmental area. We then compared the functional effects of anterior versus posterior mOFC excitotoxic lesions on tests of Pavlovian-instrumental transfer, instrumental outcome devaluation and outcome-specific reinstatement. We found evidence that the anterior mOFC had greater connectivity with the accumbens core and greater functional involvement in goal-directed action than the posterior mOFC. Consistent with previous findings across species, therefore, these results suggest that the anterior and posterior mOFC of the rat are indeed functionally distinct, and that it is the anterior mOFC that is particularly critical for inferring unobservable action outcomes.

Inhibitory Pavlovian-instrumental transfer in humans.

Although there has been extensive research in both humans and rodents regarding the influence of excitatory predictions on action selection, the influence of inhibitory reward predictions is less well understood. We used a feature-negative conditioned inhibition procedure to generate Pavlovian excitors and inhibitors, predicting the presence or absence of specific outcomes, and assessed their influence on action selection using a Pavlovian-instrumental transfer test. Inhibitors predicting the absence of a specific outcome reversed the bias in action selection elicited by outcome-specific excitors; whereas excitors promoted responding on the action associated with the same outcome as the cue, inhibitors shifted responding away from such actions and toward other actions. Furthermore, the influence of the inhibitors on choice reflected the nature of the inhibitory associations learned by participants; those encoding outcome-specific inhibitory associations showed a strong reversal in the bias elicited by the excitors, selectively biasing performance away from the action associated with the to-be-omitted outcome and toward other actions. In contrast, those encoding only general inhibitory associations did not show any bias during the transfer test and instead reduced their performance of both actions. (PsycINFO Database Record

The effect of conditioned inhibition on the specific Pavlovian-instrumental transfer effect.

Four experiments examined the effect of Pavlovian conditioned inhibition on specific Pavlovian-instrumental transfer (PIT) in human participants. The task comprised an instrumental phase in which 2 responses (R1, R2) were each paired with 1 of 2 outcomes (O1, O2: R1→O1, R2→O2), and a Pavlovian phase, in which 2 conditioned stimuli (CSs), CS1 and CS2 each signaled 1 of the 2 outcomes (CS1→O1, CS2→O2). In Experiments 1-2 a conditioned inhibitor, X, predicted the omission of 1 of the outcomes (e.g., CS1→O1, CS1X→nothing). In a subsequent test, performance of R1 and R2 was examined in the presence of CS1 and CS2. A specific PIT effect was observed: R1 was performed more than R2 during CS1, and R2 more than R1 during CS2. This PIT effect was significantly reduced by the presence of the inhibitor X in Experiment 1, in which the Pavlovian phase followed the instrumental phase, and in Experiment 2 in which it preceded it. No such effect was observed when X was presented in the absence of any expectation of the outcomes during the PIT test (Experiment 3a), or when X was trained as a signal for an alternative outcome (Experiment 3b). These results are consistent with the suggestion that the specific PIT effect occurs through a stimulus-outcome-response (S-O-R) mechanism, according to which the CS evokes a representation of the outcome which in turn elicits the response (e.g., CS1→O1→R1). The conditioned inhibitor suppresses performance of the response by suppressing activation of the outcome representation.

Basolateral amygdala rapid glutamate release encodes an outcome-specific representation vital for reward-predictive cues to selectively invigorate reward-seeking actions.

Environmental stimuli have the ability to generate specific representations of the rewards they predict and in so doing alter the selection and performance of reward-seeking actions. The basolateral amygdala participates in this process, but precisely how is unknown. To rectify this, we monitored, in near-real time, basolateral amygdala glutamate concentration changes during a test of the ability of reward-predictive cues to influence reward-seeking actions (Pavlovian-instrumental transfer). Glutamate concentration was found to be transiently elevated around instrumental reward seeking. During the Pavlovian-instrumental transfer test these glutamate transients were time-locked to and correlated with only those actions invigorated by outcome-specific motivational information provided by the reward-predictive stimulus (i.e., actions earning the same specific outcome as predicted by the presented CS). In addition, basolateral amygdala AMPA, but not NMDA glutamate receptor inactivation abolished the selective excitatory influence of reward-predictive cues over reward seeking. These data the hypothesis that transient glutamate release in the BLA can encode the outcome-specific motivational information provided by reward-predictive stimuli.

Ventral pallidal projections to mediodorsal thalamus and ventral tegmental area play distinct roles in outcome-specific Pavlovian-instrumental transfer.

Outcome-specific Pavlovian-instrumental transfer (PIT) demonstrates the way that reward-related cues influence choice between instrumental actions. The nucleus accumbens shell (NAc-S) contributes critically to this effect, particularly through its output to the rostral medial ventral pallidum (VP-m). Using rats, we investigated in two experiments the role in the PIT effect of the two major outputs of this VP-m region innervated by the NAc-S, the mediodorsal thalamus (MD) and the ventral tegmental area (VTA). First, two retrograde tracers were injected into the MD and VTA to compare the neuronal activity of the two populations of projection neurons in the VP-m during PIT relative to controls. Second, the functional role of the connection between the VP-m and the MD or VTA was assessed using asymmetrical pharmacological manipulations before a PIT test. It was found that, whereas neurons in the VP-m projecting to the MD showed significantly more neuronal activation during PIT than those projecting to the VTA, neuronal activation of these latter neurons correlated with the size of the PIT effect. Disconnection of the two pathways during PIT also revealed different deficits in performance: disrupting the VP-m to MD pathway removed the response biasing effects of reward-related cues, whereas disrupting the VP-m to VTA pathway preserved the response bias but altered the overall rate of responding. The current results therefore suggest that the VP-m exerts distinct effects on the VTA and MD and that these latter structures mediate the motivational and cognitive components of specific PIT, respectively.

Stress increases cue-triggered "wanting" for sweet reward in humans.

Stress can increase reward pursuits: This has traditionally been seen as an attempt to relieve negative affect through the hedonic properties of a reward. However, reward pursuit is not always proportional to the pleasure experienced, because reward processing involves distinct components, including the motivation to obtain a reward (i.e., wanting) and the hedonic pleasure during the reward consumption (i.e., liking). Research conducted on rodents demonstrates that stress might directly amplify the cue-triggered wanting, suggesting that under stress wanting can be independent from liking. Here, we aimed to test whether a similar mechanism exists in humans. We used analog of a Pavlovian-Instrumental Transfer test (PIT) with an olfactory reward to measure the cue triggered wanting for a reward but also the sensory hedonic liking felt during the consumption of the same reward. The analog of a PIT procedure, in which participants learned to associate a neutral image and an instrumental action with a chocolate odor, was combined with either a stress-inducing or stress-free behavioral procedure. Results showed that compared with participants in the stress-free condition, those in the stress condition mobilized more effort in instrumental action when the reward-associated cue was displayed, even though they did not report the reward as being more pleasurable. These findings suggest that, in humans, stress selectively increases cue-triggered wanting, independently of the hedonic properties of the reward. Such a mechanism supports the novel explanation proposed by animal research as to why stress often produces cue-triggered bursts of binge eating, relapses in drug addiction, or gambling.

δ-Opioid and Dopaminergic Processes in Accumbens Shell Modulate the Cholinergic Control of Predictive Learning and Choice

Decision-making depends on the ability to extract predictive information from the environment to guide future actions. Outcome-specific Pavlovian-instrumental transfer (PIT) provides an animal model of this process in which a stimulus predicting a particular outcome biases choice toward actions earning that outcome. Recent evidence suggests that cellular adaptations of δ-opioid receptors (DORs) on cholinergic interneurons (CINs) in the nucleus accumbens shell (NAc-S) are necessary for PIT. Here we found that modulation of DORs in CINs critically influences D1-receptor (D1R)-expressing projection neurons in the NAc-S to promote PIT. First, we assessed PIT-induced changes in signaling processes in dopamine D1- and D2-receptor-expressing neurons using drd2-eGFP mice, and found that PIT-related signaling was restricted to non-D2R-eGFP-expressing neurons, suggesting major involvement of D1R-neurons. Next we confirmed the role of D1Rs pharmacologically: the D1R antagonist SCH-23390, but not the D2R antagonist raclopride, infused into the NAc-S abolished PIT in rats, an effect that depended on DOR activity. Moreover, asymmetrical infusion of SCH-23390 and the DOR antagonist naltrindole into the NAc-S also abolished PIT. DOR agonists were found to sensitize the firing responses of CINs in brain slices prepared immediately after the PIT test. We confirmed the opioid-acetylcholinergic influence over D1R-neurons by selectively blocking muscarinic M4 receptors in the NAc-S, which tightly regulate the activity of D1Rs, a treatment that rescued the deficit in PIT induced by naltrindole. We describe a model of NAc-S function in which DORs modulate CINs to influence both D1R-neurons and stimulus-guided choice between goal-directed actions.

Learning-Related Translocation of δ-Opioid Receptors on Ventral Striatal Cholinergic Interneurons Mediates Choice between Goal-Directed Actions

The ability of animals to extract predictive information from the environment to inform their future actions is a critical component of decision-making. This phenomenon is studied in the laboratory using the pavlovian-instrumental transfer protocol in which a stimulus predicting a specific pavlovian outcome biases choice toward those actions earning the predicted outcome. It is well established that this transfer effect is mediated by corticolimbic afferents on the nucleus accumbens shell (NAc-S), and recent evidence suggests that δ-opioid receptors (DORs) play an essential role in this effect. In DOR-eGFP knock-in mice, we show a persistent, learning-related plasticity in the translocation of DORs to the somatic plasma membrane of cholinergic interneurons (CINs) in the NAc-S during the encoding of the specific stimulus-outcome associations essential for pavlovian-instrumental transfer. We found that increased membrane DOR expression reflected both stimulus-based predictions of reward and the degree to which these stimuli biased choice during the pavlovian-instrumental transfer test. Furthermore, this plasticity altered the firing pattern of CINs increasing the variance of action potential activity, an effect that was exaggerated by DOR stimulation. The relationship between the induction of membrane DOR expression in CINs and both pavlovian conditioning and pavlovian-instrumental transfer provides a highly specific function for DOR-related modulation in the NAc-S, and it is consistent with an emerging role for striatal CIN activity in the processing of predictive information. Therefore, our results reveal evidence of a long-term, experience-dependent plasticity in opioid receptor expression on striatal modulatory interneurons critical for the cognitive control of action.

The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian–instrumental transfer task in rats

Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Adult male Long-Evans rats were given conditioned inhibition (A+/AX-) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to D-amphetamine (2mg/kg daily injections for 7days) or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50% of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever pressing on BX trials and reduced lever pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food cup approach. Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor by enhancing the excitation of conditioned stimuli and reducing the inhibition of conditioned inhibitors.

The effects of acute stress on Pavlovian-instrumental transfer in rats

Pavlovian stimuli invigorate ongoing instrumental action, a phenomenon termed the Pavlovian-instrumental transfer (PIT) effect. Acute stressors can markedly enhance the release of corticotropin-releasing factor (CRF), and CRF injection into the nucleus accumbens increases the PIT effect. However, it is unknown whether acute stressors by themselves would amplify the PIT effect. Here, we examined the effects of acute stressors on PIT. Rats first received Pavlovian and instrumental training, and then the impact of the Pavlovian stimuli on instrumental responding was analyzed in the subsequent PIT test. Acute stressors were applied prior to the PIT test. Because the effects of acute stressors critically depend on stressor type and time of day, we used two acute stressors that involved one or several distinct stressors (denoted here as "single" vs. "multiple" stressors) applied either in the light or the dark period of the light:dark cycle. The results revealed that single and multiple stressors applied in the light period did not alter the PIT effect--that is, the ability of an appetitive Pavlovian stimulus to enhance leverpressing--or the basal leverpress rate. When applied in the dark period, single and multiple stressors also did not alter the PIT effect, but they did markedly reduce the basal leverpress rate. Diazepam pretreatment did not counteract the declines in basal instrumental responding in the PIT test that were induced by either a single or multiple stressors. Our findings suggest that acute stressors were unable to amplify the incentive salience of reward-predictive Pavlovian stimuli to activate instrumental responding, but, depending on the time of day of stressor exposure, they did reduce basal instrumental responding.

The role of melanin‐concentrating hormone in conditioned reward learning

The orexigenic neuropeptide melanin-concentrating hormone (MCH) is well positioned to play a key role in connecting brain reward and homeostatic systems due to its synthesis in hypothalamic circuitry and receptor expression throughout the cortico-striatal reward circuit. Here we examined whether targeted-deletion of the MCH receptor (MCH-1R) in gene-targeted heterozygote and knockout mice (KO), or systemic treatment with pharmacological agents designed to antagonise MCH-1R in C57BL/6J mice would disrupt two putative consequences of reward learning that rely on different neural circuitries: conditioned reinforcement (CRf) and Pavlovian-instrumental transfer (PIT). Mice were trained to discriminate between presentations of a reward-paired cue (CS+) and an unpaired CS-. Following normal acquisition of the Pavlovian discrimination in all mice, we assessed the capacity for the CS+ to act as a reinforcer for new nose-poke learning (CRf). Pharmacological disruption in control mice and genetic deletion in KO mice impaired CRf test performance, suggesting MCH-1R is necessary for initiating and maintaining behaviors that are under the control of conditioned reinforcers. To examine a dissociable form of reward learning (PIT), a naïve group of mice were trained in separate Pavlovian and instrumental lever training sessions followed by the PIT test. For all mice the CS+ was capable of augmenting ongoing lever responding relative to CS- periods. These results suggest a role for MCH in guiding behavior based on the conditioned reinforcing value of a cue, but not on its incentive motivational value.

The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

Repeated exposure to psychostimulants alters behavioral responses to reward-related cues; however, the motivational underpinnings of this effect have not been fully characterized. The following study was designed to examine how amphetamine sensitization affects performance in rats on a series of Pavlovian and operant tasks that distinguish between general-incentive and outcome-selective forms of conditioned responses. Adult male rats underwent Pavlovian and instrumental training for food pellet rewards. Following training, rats were sensitized to D-amphetamine (2 mg/kg for 7 days). Rats were subsequently tested on an outcome-selective Pavlovian-instrumental transfer (PIT) task, an outcome-reinstatement task, and an outcome devaluation task. Additionally, in a separate experiment, PIT was assessed in amphetamine-sensitized and control rats using a Pavlovian backward-conditioned stimulus. Repeated amphetamine exposure sensitized locomotor activity to acute amphetamine challenge. Amphetamine altered responses to CS presentations by increasing conditioned approach. During tests of PIT, amphetamine-treated rats showed no outcome-selectivity in their responding, responding to a CS whether or not it shared a common outcome with the instrumental response. No effect of amphetamine sensitization was observed on tests of outcome-selective reinstatement by outcome delivery or action selection based on outcome value. Amphetamine-sensitized rats showed impaired outcome-selective PIT to a backward CS but were unaltered in conditioned approach. Amphetamine sensitization prevents outcome-selective responding during PIT, which is dissociable from amphetamine's effects on conditioned approach. These data suggest fundamental alterations in how stimuli motivate action in addiction.

The general and outcome-specific forms of Pavlovian-instrumental transfer are differentially mediated by the nucleus accumbens core and shell.

Tests of Pavlovian-instrumental transfer (PIT) demonstrate that reward-predictive stimuli can exert a powerful motivational influence on the performance of instrumental actions. Recent evidence suggests that predictive stimuli produce this effect through either the general arousal (general PIT) or the specific predictions (outcome-specific PIT) produced by their association with reward. In two experiments, we examined the effects of pretraining lesions (Experiment 1) or muscimol-induced inactivation (Experiment 2) of either the core or shell regions of the nucleus accumbens (NAC) on these forms of PIT. Rats received Pavlovian training in which three auditory stimuli each predicted the delivery of a distinct food outcome. Separately, the rats were trained to perform two instrumental actions, each of which earned one of the outcomes used in Pavlovian conditioning. Finally, the effects of the three stimuli on performance of the two actions were assessed in extinction. Here we report evidence of a double dissociation between general and outcome-specific PIT at the level of the accumbens. Shell lesions eliminated outcome-specific PIT but spared general PIT, whereas lesions of the core abolished general PIT but spared outcome-specific PIT. Importantly, the infusion of muscimol into core or shell made immediately before the PIT tests produced a similar pattern of results. These results suggest that whereas the NAC core mediates the general excitatory effects of reward-related cues, the NAC shell mediates the effect of outcome-specific reward predictions on instrumental performance, and thereby serve to clarify reported discrepancies regarding the role of the NAC core and shell in PIT.

Neuronal correlates of normal and drug‐potentiated Pavlovian–instrumental transfer (Commentary on Saddoris et al.)

As Saddoris et al. (2011) emphasized in their exciting new study, reward-directed actions are often initiated or facilitated by conditional stimuli that have been independently associated with the reward. The influence of conditional cues over action is also thought to play a major role in drug addiction. Yet, vital as this process may be to learned behavior, it is a difficult one to isolate experimentally, and little is known about its mechanism at the level of neuronal activity. Here, the authors make new headway on the issue by measuring neural firing correlates of Pavlovian–instrumental transfer (PIT) in rats. The basic effect of PIT can perhaps be traced back to Estes (Estes, 1943, 1948), and is revealed by a three-phase protocol: (i) train an animal to associate a Pavlovian positive conditioned stimulus (CS+) cue, such as a tone, with reward; (ii) separately train the animal to associate an instrumental action, such as a lever press, with the reward; and (iii) present the CS+ with the levers available. In this last test phase, the animal will press the lever much more when the CS+ is presented, despite never having ‘learned’ this cue-press sequence as a means of obtaining a reward. Thus, the PIT test is able to isolate the invigoration of actions by independently learned Pavlovian stimuli. Saddoris et al. (2011) trained rats following this protocol, and also included a non-predictive CS− cue and an unrewarded lever as controls. On the PIT test day, firing of projection neurons was recorded in the nucleus accumbens core and shell, which are key substrates for the effect (Wyvell & Berridge, 2000; Corbit et al., 2001; Hall et al., 2001; Lex & Hauber, 2008). Behaviorally, the CS+ increased lever pressing, as confirmation of PIT. Neurally, many interesting accumbens firing differences are reported between direction of responses, stimuli evoking them, and recording sites, further building a view of substantial heterogeneity and information multiplexing in accumbens firing. A main finding to highlight was that PIT performance levels correlated with the number of core neurons that fired more to the CS+ than to the CS− or pre-cue baseline and with the number of shell neurons that fired during lever pressing more robustly when the CS+ was present (i.e. PIT-modulated). This potentially indicates a distinct contribution for the core in assigning motivational value to reward-predictive cues to arouse behavior, and for the shell in integrating learned cue and action information to guide PIT performance. In a separate experiment, rats underwent a period of cocaine self-administration after the learning phases, which led them, in the PIT test, to press even more during the CS+ than control groups. The clear PIT enhancement coincided with a similarly clear increase in the number of shell (but not core) neurons firing more to rewarded versus unrewarded stimuli and actions, as well as in the number of PIT-modulated neurons in both shell and core. Food cup entry and related firing was unaffected, bolstering the conclusion that firing reflected PIT rather than general reward pursuit or psychomotor activation. Thus, it would seem that these data reveal elements of firing plasticity that could contribute to the influence of dopamine on PIT (Dickinson et al., 2000; Wyvell & Berridge, 2000; Lex & Hauber, 2008), and to the inflated capacity of independently learned cues to motivate reward seeking in addiction states (Wyvell & Berridge, 2001). One suspects, on the basis of the many brain sites implicated in PIT, that the accumbens is contributing particular component features. Determining what functional coding features emerge in these other sites would be key to fleshing out the effect at a circuit level (Homayoun & Moghaddam, 2009), but it is a challenge, as sites for PIT span mesocorticolimbic and sensorimotor circuitry (e.g. see Holland & Petrovich, 2005; Yin et al., 2008). This effort might be aided by multisite recordings or targeted online manipulations of key firing patterns to causally control PIT, as well as task designs to dissociate general from outcome-specific forms of PIT (Blundell et al., 2001; Corbit & Balleine, 2005). For now, however, this work represents an important and ‘motivating’ step forwards.

Double Dissociation of Basolateral and Central Amygdala Lesions on the General and Outcome-Specific Forms of Pavlovian-Instrumental Transfer

This series of experiments compared the effects of lesions of the basolateral complex (BLA) and the central nucleus (CN) of the amygdala on a number of tests of instrumental learning and performance and particularly on the contribution of these structures to the specific and general forms of pavlovian-instrumental transfer (PIT). In experiment 1, groups of BLA-, CN-, and sham-lesioned rats were first trained to press two levers, each earning a unique food outcome (pellets or sucrose), after which they were given training in which two auditory stimuli (tone and white noise) were paired with these same outcomes. Tests of specific satiety induced outcome devaluation, and tests of PIT revealed that, although the rats in all of the groups performed similarly during both the instrumental and pavlovian acquisition phases, BLA, but not CN, lesions abolished selective sensitivity to a change in the reward value of the instrumental outcome as well as to the selective excitatory effects of reward-related cues in PIT. In experiment 2, we developed a procedure in which both the general motivational and the specific excitatory effects of pavlovian cues could be assessed in the same animal and found that BLA lesions abolished the outcome-specific but spared the general motivational effects of pavlovian cues. In contrast, lesions of CN abolished the general motivational but spared the specific effects of these cues. Together, these results suggest that the BLA mediates outcome-specific incentive processes, whereas CN is involved in controlling the general motivational influence of reward-related events.

The Role of the Nucleus Accumbens in Instrumental Conditioning: Evidence of a Functional Dissociation between Accumbens Core and Shell

In three experiments we examined the effect of bilateral excitotoxic lesions of the nucleus accumbens core or shell subregions on instrumental performance, outcome devaluation, degradation of the instrumental contingency, Pavlovian conditioning, and Pavlovian-instrumental transfer. Rats were food deprived and trained to press two levers, one delivering food pellets and the other a sucrose solution. All animals acquired the lever-press response although the rate of acquisition and overall response rates in core-lesioned animals were depressed relative to that in the shell- or sham-lesioned animals. Furthermore, in shell- and sham-lesioned rats, post-training devaluation of one of the two outcomes using a specific satiety procedure produced a selective reduction in performance on the lever that, in training, delivered the prefed outcome. In contrast, the core-lesioned rats failed to show a selective devaluation effect and reduced responding on both levers. Subsequent tests revealed that these effects of core lesions were not caused by an impairment in their ability to recall the devalued outcome, to discriminate the two outcomes, or to encode the instrumental action-outcome contingencies to which they were exposed. Additionally, the core lesions did not have any marked effect on Pavlovian conditioning or on Pavlovian-instrumental transfer. Importantly, although shell-lesioned rats showed no deficit in any test of instrumental conditioning or in Pavlovian conditioning, they failed to show any positive transfer in the Pavlovian-instrumental transfer test. This double dissociation suggests that nucleus accumbens core and shell differentially mediate the impact of instrumental and Pavlovian incentive processes, respectively, on instrumental performance.