Appetitive Conditioned Stimulus Research Articles

The role of context conditioning in the reinstatement of responding to an alcohol-predictive conditioned stimulus

Re-exposure to an unconditioned stimulus (US) can reinstate extinguished conditioned responding elicited by a conditioned stimulus (CS). We tested the hypothesis that the reinstatement of responding to an appetitive CS is driven by an excitatory association formed between the US and the context that the US was ingested in during US re-exposure. Male, Long-Evans rats were acclimated to drinking alcohol (15%, v/v) in the home-cage, then trained to associate an auditory CS with an alcohol-US that was delivered into a fluid port for oral intake. During subsequent extinction sessions, the CS was presented as before, but without alcohol. After extinction, rats were re-exposed to alcohol as in training, but without the CS (alcohol re-exposure). 24 h later at test, the CS was presented as in training, but without alcohol. First, we tested the effect of extinguishing the context-alcohol association, formed during alcohol re-exposure, on reinstatement. Conducting four context extinction sessions across four days (spaced extinction) after the alcohol re-exposure session did not impact reinstatement. However, four context extinction sessions conducted across two days (massed extinction) prevented reinstatement. Next, we conducted alcohol re-exposure in a context that either differed from, or was the same as, the test context. One alcohol re-exposure session in a different context did not affect reinstatement, however, three alcohol re-exposure sessions in a different context significantly reduced reinstatement during the first CS trial. These results partially support the view that a context-US association formed during US re-exposure drives the reinstatement of responding to an appetitive, alcohol-predictive CS.

Context controls the timing of responses to an alcohol-predictive conditioned stimulus

Context can influence the number of responses elicited by a discrete, appetitive conditioned stimulus (CS) but can context control when a CS elicits a response? To test this fundamental question, we gave male, Long-Evans rats Pavlovian conditioning sessions in which the same auditory conditioned stimulus (CS, 30 s, 15 trials/session) was presented in 2 different physical contexts on alternating days, according to a within-subjects design. In one context, called the early context, alcohol (15 % ethanol, 0.2 ml/trial) was delivered from the onset of the 5th second until the termination of the 10th second of the 30 s CS. In the second late context, alcohol was delivered from the onset of the 25th second until the termination of the 30th second of the same CS. In a comparison of the last session of training, the probability of making a conditioned response during the first four seconds of the CS was significantly higher in the early context than in the late context. This result shows that context can signal when an unconditioned stimulus occurs in relation to a CS and highlights a role for context in controlling precisely timed alcohol-seeking responses.

Optogenetic Activation of the Basolateral Amygdala Promotes Both Appetitive Conditioning and the Instrumental Pursuit of Reward Cues.

Reward-associated stimuli can both evoke conditioned responses and acquire reinforcing properties in their own right, becoming avidly pursued. Such conditioned stimuli (CS) can guide reward-seeking behavior in adaptive (e.g., locating food) and maladaptive (e.g., binge eating) ways. The basolateral amygdala (BLA) regulates conditioned responses evoked by appetitive CS, but less is known about how the BLA contributes to the instrumental pursuit of CS. Here we studied the influence of BLA neuron activity on both behavioral effects. Water-restricted male rats learned to associate a light-tone cue (CS) with water delivery into a port. During these Pavlovian conditioning sessions, we paired CS presentations with photo-stimulation of channelrhodopsin-2 (ChR2)-expressing BLA neurons. BLA photo-stimulation potentiated CS-evoked port entries during conditioning, indicating enhanced conditioned approach and appetitive conditioning. Next, new rats received Pavlovian conditioning without photo-stimulation. These rats then received instrumental conditioning sessions where they could press an inactive lever or an active lever that produced CS presentation, without water delivery. Rats pressed more on the active versus inactive lever, and pairing CS presentation with BLA-ChR2 photo-stimulation intensified responding for the CS. This suggests that BLA-ChR2 photo-stimulation enhanced CS incentive value. In a separate experiment, rats did not reliably self-administer BLA-ChR2 stimulations, suggesting that BLA neurons do not carry a primary reward signal. Last, intra-BLA infusions of d-amphetamine also intensified lever-pressing for the CS. The findings suggest that BLA-mediated activity facilitates CS control over behavior by enhancing both appetitive Pavlovian conditioning and instrumental pursuit of CS.SIGNIFICANCE STATEMENT Cues paired with rewards can guide animals to valuable resources such as food. Cues can also promote dysfunctional reward-seeking behavior, as in overeating. Reward-paired cues influence reward seeking through two major mechanisms. First, reward-paired cues evoke conditioned anticipatory behaviors to prepare for impending rewards. Second, reward-paired cues are powerful motivators and they can evoke pursuit in their own right. Here we show that increasing neural activity in the basolateral amygdala enhances both conditioned anticipatory behaviors and pursuit of reward-paired cues. The basolateral amygdala therefore facilitates cue-induced control over behavior by both increasing anticipation of impending rewards and making reward cues more attractive.

The Emergence of a Stable Neuronal Ensemble from a Wider Pool of Activated Neurons in the Dorsal Medial Prefrontal Cortex during Appetitive Learning in Mice.

Animals selectively respond to environmental cues associated with food reward to optimize nutrient intake. Such appetitive conditioned stimulus-unconditioned stimulus (CS-US) associations are thought to be encoded in select, stable neuronal populations or neuronal ensembles, which undergo physiological modifications during appetitive conditioning. These ensembles in the medial prefrontal cortex (mPFC) control well-established, cue-evoked food seeking, but the mechanisms involved in the genesis of these ensembles are unclear. Here, we used male Fos-GFP mice that express green fluorescent protein (GFP) in recently behaviorally activated neurons, to reveal how dorsal mPFC neurons are recruited and modified to encode CS-US memory representations using an appetitive conditioning task. In the initial conditioning session, animals did not exhibit discriminated, cue-selective food seeking, but did so in later sessions indicating that a CS-US association was established. Using microprism-based in vivo 2-Photon imaging, we revealed that only a minority of neurons activated during the initial session was consistently activated throughout subsequent conditioning sessions and during cue-evoked memory recall. Notably, using ex vivo electrophysiology, we found that neurons activated following the initial session exhibited transient hyperexcitability. Chemogenetically enhancing the excitability of these neurons throughout subsequent conditioning sessions interfered with the development of reliable cue-selective food seeking, indicated by persistent, nondiscriminated performance. We demonstrate how appetitive learning consistently activates a subset of neurons to form a stable neuronal ensemble during the formation of a CS-US association. This ensemble may arise from a pool of hyperexcitable neurons activated during the initial conditioning session.SIGNIFICANCE STATEMENT Appetitive conditioning endows cues associated with food with the ability to guide food-seeking, through the formation of a food-cue association. Neuronal ensembles in the mPFC control established cue-evoked food-seeking. However, how neurons undergo physiological modifications and become part of an ensemble during conditioning remain unclear. We found that only a minority of dorsal mPFC neurons activated on the initial conditioning session became consistently activated during conditioning and memory recall. These initially activated neurons were also transiently hyperexcitable. We demonstrate the following: (1) how stable neuronal ensemble formation in the dorsal mPFC underlies appetitive conditioning; and (2) how this ensemble may arise from hyperexcitable neurons activated before the establishment of cue-evoked food seeking.

Strong seduction: impulsivity and the impact of contextual cues on instrumental behavior in alcohol dependence

Alcohol-related cues acquire incentive salience through Pavlovian conditioning and then can markedly affect instrumental behavior of alcohol-dependent patients to promote relapse. However, it is unclear whether similar effects occur with alcohol-unrelated cues. We tested 116 early-abstinent alcohol-dependent patients and 91 healthy controls who completed a delay discounting task to assess choice impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice behavior, we tiled the background of the computer screen either with conditioned stimuli (CS) previously generated by pairing abstract pictures with pictures indicating monetary gains or losses, or with pictures displaying alcohol or water beverages. CS paired to money gains and losses affected instrumental choices differently. This PIT effect was significantly more pronounced in patients compared to controls, and the group difference was mainly driven by highly impulsive patients. The PIT effect was particularly strong in trials in which the instrumental stimulus required inhibition of instrumental response behavior and the background CS was associated to monetary gains. Under that condition, patients performed inappropriate approach behavior, contrary to their previously formed behavioral intention. Surprisingly, the effect of alcohol and water pictures as background stimuli resembled that of aversive and appetitive CS, respectively. These findings suggest that positively valenced background CS can provoke dysfunctional instrumental approach behavior in impulsive alcohol-dependent patients. Consequently, in real life they might be easily seduced by environmental cues to engage in actions thwarting their long-term goals. Such behaviors may include, but are not limited to, approaching alcohol.

Basolateral amygdala nucleus responses to appetitive conditioned stimuli correlate with variations in conditioned behaviour.

In the lateral amygdala (LA), training-induced increases in neuronal responsiveness to conditioned stimuli (CSs) reflect potentiated sensory responses that drive conditioned behaviours (CRs) via LA's targets. The basolateral nucleus of the amygdala (BL) receives LA inputs and projects to various subcortical sites that can drive aversive and appetitive CRs. Consistent with this, BL neurons also develop increased responses to CSs that predict rewarding or aversive outcomes. This increased BL activity is thought to reflect the potentiated sensory responses of LA neurons. Here we contrast the CS-related activity of BL neurons when rats produced the expected CR or not, to show that cells activated by appetitive CSs mainly encode behavioural output, not CS identity. The strong dependence of BL activity on behaviour irrespective of CS identity suggests that feedforward connectivity from LA to BL can be overridden by other BL inputs.

Discriminative evaluative conditioning in the long-term after severe accidental injury

Impairments in classical fear conditioning and deficits in discriminative learning are observed in posttraumatic stress disorder (PTSD). However, it is unknown whether similar impairments can be found with types of discriminative learning other than classical conditioning, such as evaluative conditioning (EC), in which the valence of a stimulus can be transferred to other stimuli. In this study, we investigated whether EC is also influenced by traumatic experiences independently of presence of PTSD. We tested 14 accident survivors with remitted PTSD, 14 survivors without PTSD, and 16 non-trauma controls. We used behavioral measures, psychophysiological indicators, and subjective ratings for tasks. General effects of learning were observed across groups and conditioning/extinction. Trauma controls had slower reaction times (RTs) to the aversive conditioned stimulus compared to appetitive conditioned and neutral stimuli, as well as slower RTs and increased accuracy during conditioning than during extinction. Remitted PTSD participants showed opposite results, demonstrating decreased accuracy and slower RTs during conditioning as compared to during extinction. No discriminative effect was found in the non-trauma controls and the remitted PTSD participants. These results suggest that a traumatic experience influences EC, and that this influence differs between individuals who have and have not developed PTSD after traumatic exposure.

An appetitive conditioned stimulus enhances fear acquisition and impairs fear extinction.

Four experiments used between- and within-subject designs to examine appetitive–aversive interactions in rats. Experiments 1 and 2 examined the effect of an excitatory appetitive conditioned stimulus (CS) on acquisition and extinction of conditioned fear. In Experiment 1, a CS shocked in a compound with an appetitive excitor (i.e., a stimulus previously paired with sucrose) underwent greater fear conditioning than a CS shocked in a compound with a neutral stimulus. Conversely, in Experiment 2, a CS extinguished in a compound with an appetitive excitor underwent less extinction than a CS extinguished in a compound with a neutral stimulus. Experiments 3 and 4 compared the amount of fear conditioning to an appetitive excitor and a familiar but neutral target CS when the compound of these stimuli was paired with shock. In each experiment, more fear accrued to the appetitive excitor than to the neutral CS. These results show that an appetitive excitor influences acquisition and extinction of conditioned fear to a neutral CS and itself undergoes a greater associative change than the neutral CS across compound conditioning. They are discussed with respect to the role of motivational information in regulating an associative change in appetitive–aversive interactions.

Effects of sucrose concentration and water deprivation on Pavlovian conditioning and responding for conditioned reinforcement.

An appetitive Pavlovian conditioned stimulus (CS) can predict an unconditioned stimulus (US) and acquire incentive salience. We tested the hypothesis that US intensity and motivational state of the subject would influence Pavlovian learning and impact the attribution of incentive salience to an appetitive Pavlovian CS. To this end, we examined the effects of sucrose concentration and water deprivation on the acquisition of Pavlovian conditioning and responding for a conditioned reinforcer. Male Long-Evans rats (Harlan; 220-240 g) receiving 3% (3S) or 20% (20S) sucrose were either non-water deprived or given water for 1 hr per day. During Pavlovian conditioning sessions, half the rats in each concentration and deprivation condition received a 10-s CS paired with 0.2 ml of sucrose (16 trials/session; 3.2 ml/session). The remainder received unpaired CS and US presentations. Entries into a port where sucrose was delivered were recorded. Next, responding for conditioned reinforcement was tested, wherein pressing an active lever produced the CS and pressing an inactive lever had no consequences. CS-elicited port entries increased, and latency to the first CS-elicited port entry decreased across sessions in paired groups. Water deprivation augmented these effects, whereas sucrose concentration had no significant impact on behavior. Responding for conditioned reinforcement was observed in the 20S water-deprived, paired group. Thus, water deprivation can facilitate the acquisition of Pavlovian conditioning, potentially by enhancing motivational state, and a high-intensity US and a high motivational state can interact to heighten the attribution of incentive salience to an appetitive Pavlovian CS. (PsycINFO Database Record

Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats

The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03nmol muscimol; 0.3nmol baclofen; 0.3μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted.

Appetitive cue-evoked ERK signaling in the nucleus accumbens requires NMDA and D1 dopamine receptor activation and regulates CREB phosphorylation.

Conditioned stimuli (CS) can modulate reward-seeking behavior. This modulatory effect can be maladaptive and has been implicated in excessive reward seeking and relapse to drug addiction. We previously demonstrated that exposure to an appetitive CS causes an increase in the activation of extracellular signal-regulated kinase (ERK) and cyclic-AMP response-element binding protein (CREB) in the nucleus accumbens (NAc) of rats, and that CS-evoked ERK activation is critical for CS control over reward seeking. To elucidate the mechanism that mediates CS-driven ERK activation in the NAc, we selectively blocked NMDA glutamate or D1 dopamine receptors in the NAc. To determine whether CS-driven ERK and CREB activation are linked, we selectively blocked ERK signaling in the NAc. We found that both NMDA and D1 receptors are critical for CS-driven ERK signaling in the NAc, and that this recruitment of the ERK cascade is responsible for increased CREB activation in the presence of the CS. Our findings suggest that activation of the NMDAR-D1R/ERK/CREB signal transduction pathway plays a critical role in the control of reward-seeking behavior by reward-predictive cues.

Effect of flumethrin on survival and olfactory learning in honeybees.

Flumethrin has been widely used as an acaricide for the control of Varroa mites in commercial honeybee keeping throughout the world for many years. Here we test the mortality of the Asian honeybee Apis cerana cerana after treatment with flumethrin. We also ask (1) how bees react to the odor of flumethrin, (2) whether its odor induces an innate avoidance response, (3) whether its taste transmits an aversive reinforcing component in olfactory learning, and (4) whether its odor or taste can be associated with reward in classical conditioning. Our results show that flumethrin has a negative effect on Apis ceranàs lifespan, induces an innate avoidance response, acts as a punishing reinforcer in olfactory learning, and interferes with the association of an appetitive conditioned stimulus. Furthermore flumethrin uptake within the colony reduces olfactory learning over an extended period of time.

Neural correlates of appetitive–aversive interactions in Pavlovian fear conditioning

We used Pavlovian counterconditioning in rats to identify the neural mechanisms for appetitive-aversive motivational interactions. In Stage I, rats were trained on conditioned stimulus (CS)-food (unconditioned stimulus [US]) pairings. In Stage II, this appetitive CS was transformed into a fear CS via pairings with footshock. The development of fear responses was retarded in rats that had received Stage I appetitive training. This counterconditioning was associated with increased levels of phosphorylated mitogen activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions, including midline thalamus, rostral agranular insular cortex (RAIC), lateral amygdala, and nucleus accumbens core and shell, but decreased expression in the ventrolateral quadrant of the midbrain periaqueductal gray. These brain regions showing differential pMAPK-IR have previously been identified as part of the fear prediction error circuit. We then examined the causal role of RAIC MAPK in fear learning and showed that Stage II fear learning was prevented by RAIC infusions of the MEK inhibitor PD098059 (0.5 µg/hemisphere). Taken together, these results show that there are opponent interactions between the appetitive and aversive motivational systems during fear learning and that the transformation of a reward CS into a fear CS is linked to heightened activity in the fear prediction error circuit.

Over-expectation generated in a complex appetitive goal-tracking task is capable of inducing memory reconsolidation

Discrepancies in an expected outcome have been demonstrated to result in modification of behaviour in both appetitive and aversive conditioning settings. In this study, we sought to establish whether overexpectation generated from compound conditioning with two previously rewarded stimuli was able to induce memory destabilisation and subsequent reconsolidation in a Pavlovian conditioned approach setting. It was shown that 4 days, but not 1 day, of overexpectation training was required to induce memory reconsolidation, and this was disrupted by application of the NMDA subtype of glutamate receptor antagonist MK-801 prior to overexpectation training, but not by MK-801 application 6 h post-training. These data provide evidence that the memories underlying Pavlovian conditioned approach do undergo reconsolidation and that such reconsolidation can be triggered by overexpectation. Therefore, the updating of appetitive conditioned stimulus and unconditioned stimulus associations underpinning conditioned responding in manners other than extinction training is likely achieved through memory reconsolidation.

Appetitive–aversive interactions in Pavlovian fear conditioning.

The existence of value coding and salience coding neurons in the mammalian brain, including in habenula and ventral tegmental area, has sparked considerable interest in the interactions that occur between Pavlovian appetitive and aversive conditioning. Here we studied these appetitive-aversive interactions at the behavioral level by assessing the learning that occurs when a Pavlovian appetitive conditioned stimulus (conditional stimulus, CS) serves as a CS for shock in Pavlovian fear conditioning. A Pavlovian appetitive CS was retarded in the rate at which it could be transformed into a fear CS (counterconditioning), but the presence of the appetitive CS augmented fear learning to a concurrently presented neutral CS (superconditioning). Retardation of fear learning was not alleviated by manipulations designed to restore the associability of the appetitive CS before fear conditioning but was alleviated by manipulations designed to increase the aversive quality of the shock unconditioned stimulus (US). These findings are consistent with opponent interactions between the appetitive and aversive motivational systems and provide a behavioral approach for assessing the neural correlates of these appetitive-aversive interactions.

Extinction of goal tracking also eliminates the conditioned reinforcing effects of an appetitive conditioned stimulus.

Previous studies have suggested that the effects of extinction are response-specific. The present study investigated whether an extinction treatment that eliminated goal tracking elicited by an appetitive conditioned stimulus (CS) would also eliminate the conditioned reinforcing effects of that CS. Rats were first trained on a goal-tracking procedure in which an auditory CS was paired with a food unconditioned stimulus. Animals learned to approach the location where the food was delivered. In a subsequent phase, rats in one group received extinction training that eliminated the goal-tracking elicited by the CS. Rats in the other group did not experience extinction of the food-paired CS. Then, both groups received a test for conditioned reinforcement in which leverpresses resulted in the brief presentation of the stimulus previously paired with food. This stimulus did not act as a conditioned reinforcer in the group that had been subjected to extinction training, but did serve as a conditioned reinforcer in the group that did not experience extinction. These results indicate that the effects of extinction generalize from the approach-eliciting to the conditioned reinforcing effects of an appetitive CS.

Conditioned response evoked by nicotine conditioned stimulus preferentially induces c-Fos expression in medial regions of caudate-putamen.

Nicotine has both unconditioned and conditioned stimulus properties. Conditioned stimulus properties of nicotine may contribute to the tenacity of nicotine addiction. The purpose of this experiment was to use neurohistochemical analysis of rapidly developing c-Fos protein to elucidate neurobiological loci involved in the processing of nicotine as an interoceptive conditioned stimulus (CS). Rats were injected (SC) in an intermixed fashion with saline or nicotine (16 sessions of each) and placed in conditioning chambers where they were given one of the three conditions depending on group assignment: (a) nicotine paired 100% of the time with intermittent access to sucrose (nicotine-CS condition), (b) nicotine and saline each paired 50% of the time with sucrose (chamber-CS condition), or (c) no sucrose US control (CS-alone condition). Rats in the nicotine-CS condition acquired the discrimination as evidenced by goal-tracking (ie, increased dipper entries before initial sucrose delivery) only on nicotine sessions. The chamber-CS condition showed goal-tracking on all sessions; no goal-tracking was seen in the CS-alone condition. On the test day, rats in each condition were challenged with saline or nicotine and later assessed for c-Fos immunoreactivity. In concordance with previous reports, nicotine induced c-Fos expression in the majority of areas tested; however, learning-dependent expression was specific to dorsomedial and ventromedial regions of caudate-putamen (dmCPu, vmCPu). Only rats in the nicotine-CS condition, when challenged with nicotine, had higher c-Fos expression in the dmCPu and vmCPu. These results suggest that medial areas of CPu involved in excitatory conditioning with an appetitive nicotine CS.

Conditioned associations and economic decision biases

Humans show substantial deviation from rationality during economic decision making under uncertainty. A computational perspective suggests these deviations arise out of an interaction between distinct valuation systems in the brain. Here, we provide behavioural data showing that the incidental presentation of aversive and appetitive conditioned stimuli can alter subjects’ preferences in an economic task, involving a choice between a safe or gamble option. These behavioural effects informed a model-based analysis of a functional magnetic resonance imaging (fMRI) experiment, involving an identical paradigm, where we demonstrate that this conditioned behavioral bias engages the amygdala, a brain structure associated with acquisition and expression of conditioned associations. Our findings suggest that a well known bias in human economic choice can arise from an influence of conditioned associations on goal-directed decision making, consistent with an architecture of choice that invokes distinct decision-making systems.

Orbitofrontal cortex and amygdalar over-activity is associated with an inability to use the value of expected outcomes to guide behaviour in serotonin transporter knockout rats

A disturbance in 5-HT signalling can lead to maladaptive and disruptive behavioural changes seen in neuropsychiatric disorders, potentially by 5-HT’s role in cognitive control over behaviour. 5-HT levels are tightly controlled by the serotonin transporter (5-HTT). We and others have observed that 5-HTT availability affects reversal learning. Here we investigated the role of 5-HT in another type of cognitive control, which is the ability to use the value of expected outcomes to guide behaviour. 5-HTT knockout (5-HTT −/− ) rats and wild-type (5-HTT +/+ ) controls were subjected to a Pavlovian reinforcer devaluation paradigm, which assesses the ability of an appetitive conditioned stimulus (CS) to gain access to the motivational properties of an upcoming aversive unconditioned stimulus (US). Neural correlates were evaluated using c-Fos immunohistochemistry, in brains of animals sacrificed 90 min following the start of the probe test. Results show that conditioned responding was decreased in 5-HTT +/+ , but not 5-HTT −/− , rats after US devaluation. In addition, OFC and basolateral amygdala (BLA) c-Fos immunoreactivity was increased in non-devalued 5-HTT −/− rats compared to non-devalued 5-HTT +/+ rats. Whereas US devaluation increased c-Fos immunoreactivity in the OFC and BLA of 5-HTT +/+ rats, there was no further increase in c-Fos immunoreactivity in the OFC and BLA of 5-HTT −/− rats. Taken together, 5-HTT −/− rats are unable to use the value of expected outcomes to guide behaviour, potentially due to over-activity of the OFC and BLA. Our findings suggest a new modulatory role of 5-HT in cognitive control over behaviour, which may have important implications for psychopathologies, like anxiety disorders and addiction.

Central, But Not Basolateral, Amygdala Is Critical for Control of Feeding by Aversive Learned Cues

Environmental factors contribute to the motivation to eat and can override homeostatic signals to stimulate eating in sated states, or inhibit eating in states of hunger. In particular, stress, fear, and anxiety have been linked to suppression of eating and anorexia nervosa. Here, we use a rodent model of an aversive cue-induced cessation of feeding. In this setting, food-deprived rats suppress eating when presented with a tone [conditioned stimulus (CS)] that was previously paired with footshocks [unconditioned stimulus (US)]. To begin to delineate the underlying neural circuitry we examined the two regions of the amygdala with well known roles in associative learning--the central nucleus (CEA) and the basolateral area (BLA; includes the basolateral, basomedial, and lateral nuclei). We produced selective, bilateral, neurotoxic lesions of the CEA or BLA, and then trained these rats together with sham-lesioned controls in a behavioral protocol that allowed a test for food consumption in the presence of an aversive CS. Both sham- and BLA-lesioned rats showed inhibition of eating when presented with the CS. In contrast, bilateral, neurotoxic lesions of the CEA abolished this effect. These results demonstrate that the CEA, but not BLA, is critical for control of feeding by an aversive CS. Previously we demonstrated that enhancement of eating by an appetitive CS is dependent on the integrity of BLA, but not CEA. Those findings together with the current results show a double dissociation between amygdalar subsystems that control food consumption by appetitive and aversive learned cues.