Conditioned Aversive Stimuli Research Articles

Genetic dissection of the zebrafish habenula, a possible switching board for selection of behavioral strategy to cope with fear and anxiety

The habenula is a part of an evolutionarily highly conserved conduction pathway within the limbic system that connects telencephalic nuclei to the brain stem nuclei such as interpeduncular nucleus(IPN), the ventral tegmental area (VTA), and the raphe.In mammals, the medial habenula receives inputs from the septohippocampal system, and relaying such information to the IPN. In contrast, the lateral habenula receives inputs from the ventral pallidum, a part of the basal ganglia. The physical adjunction of these two habenular nuclei suggests that the habenula may act as an intersection of the neural circuits for controlling emotion and behavior. We have recently elucidated that zebrafish has the equivalent structure as the mammalian habenula. The transgenic zebrafish, in which the neural signal transmission from the lateral subnucleus of the dorsal habenula to the dorsal IPN was selectively impaired, showed extremely enhanced levels of freezing response to presentation of the conditioned aversive stimulus. Our observation supports that the habenula may act as the multimodal switching board for controlling emotional behaviors and/or memory inexperience dependent manners.

Repeated amphetamine exposure disrupts dopaminergic modulation of amygdala-prefrontal circuitry and cognitive/emotional functioning.

Repeated exposure to psychostimulants such as amphetamine (AMPH) disrupts cognitive and behavioral processes mediated by the medial prefrontal cortical (mPFC) and basolateral amygdala (BLA). The present study investigated the effects of repeated AMPH exposure on the neuromodulatory actions of dopamine (DA) on BLA-mPFC circuitry and cognitive/emotional processing mediated by these circuits. Rats received five AMPH (2 mg/kg) or saline injections (controls) over 10 d, followed by 2-4 week drug washout. In vivo neurophysiological extracellular recordings in urethane-anesthetized rats were used to obtain data from mPFC neurons that were either inhibited or excited by BLA stimulation. In controls, acute AMPH attenuated BLA-evoked inhibitory or excitatory responses; these effects were mimicked by selective D(2) or D(1) agonists, respectively. However, in AMPH-treated rats, the ability of these dopaminergic manipulations to modulate BLA-driven decreases/increases in mPFC activity was abolished. Repeated AMPH also blunted the excitatory effects of ventral tegmental area stimulation on mPFC neural firing. Behavioral studies assessed the effect of repeated AMPH on decision making with conditioned punishment, a process mediated by BLA-mPFC circuitry and mesocortical DA. These treatments impaired the ability of rats to use conditioned aversive stimuli (footshock-associated cue) to guide the direction of instrumental responding. Collectively, these data suggest that repeated AMPH exposure can lead to persistent disruption of dopaminergic modulation of BLA-mPFC circuitry, which may underlie impairments in cognitive/emotional processing observed in stimulant abusers. Furthermore, they suggest that impairments in decision making guided by aversive stimuli observed in stimulant abusers may be the result of repeated drug exposure.

The role of nucleus accumbens and dorsolateral striatal D2 receptors in active avoidance conditioning

The role of dopamine (DA) in rewarding motivated actions is well established but its role in learning how to avoid aversive events is still controversial. Here we tested the role of D2-like DA receptors in the nucleus accumbens (NAc) and the dorsolateral striatum (DLS) of rats in the learning and performance of conditioned avoidance responses (CAR). Adult male Wistar rats received systemic, intra-NAc or intra-DLS (pre- or post-training) administration of a D2-like receptor agonist (quinpirole) or antagonist ((−)sulpiride) and were given two sessions in the two-way active avoidance task. The main effects observed were: (i) sulpiride and lower (likely pre-synaptic) doses of quinpirole decreased the number of CARs and increased the number of escape failures; (ii) higher doses of quinpirole (likely post-synaptic) increased inter-trial crossings and failures; (iii) pre-training administration of sulpiride decreased the number of CARs in both training and test sessions when infused into the NAc, but this effect was observed only in the test session when it was infused into the DLS; (iv) post-training administration of sulpiride decreased CARs in the test session when infused into the NAc but not DLS. These findings suggest that activation of D2 receptors in the NAc is critical for fast adaptation to responding to unconditioned and conditioned aversive stimuli while activation of these receptors in the DLS is needed for a slower learning of how to respond to the same stimuli based on previous experiences.

Impact of infralimbic inputs on intercalated amygdala neurons: A biophysical modeling study

Intercalated (ITC) amygdala neurons regulate fear expression by controlling impulse traffic between the input (basolateral amygdala; BLA) and output (central nucleus; Ce) stations of the amygdala for conditioned fear responses. Previously, stimulation of the infralimbic (IL) cortex was found to reduce fear expression and the responsiveness of Ce neurons to BLA inputs. These effects were hypothesized to result from the activation of ITC cells projecting to Ce. However, ITC cells inhibit each other, leading to the question of how IL inputs could overcome the inter-ITC inhibition to regulate the responses of Ce neurons to aversive conditioned stimuli (CSs). To investigate this, we first developed a compartmental model of a single ITC cell that could reproduce their bistable electroresponsive properties, as observed experimentally. Next, we generated an ITC network that implemented the experimentally observed short-term synaptic plasticity of inhibitory inter-ITC connections. Model experiments showed that strongly adaptive CS-related BLA inputs elicited persistent responses in ITC cells despite the presence of inhibitory interconnections. The sustained CS-evoked activity of ITC cells resulted from an unusual slowly deinactivating K(+) current. Finally, over a wide range of stimulation strengths, brief IL activation caused a marked increase in the firing rate of ITC neurons, leading to a persistent decrease in Ce output, despite inter-ITC inhibition. Simulations revealed that this effect depended on the bistable properties and synaptic heterogeneity of ITC neurons. These results support the notion that IL inputs are in a strategic position to control extinction of conditioned fear via the activation of ITC neurons.

Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats

We found that development of obesity was coupled with the emergence of a progressively worsening brain reward deficit. Similar changes in reward homeostasis induced by cocaine or heroin is considered a critical trigger in the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2R) were downregulated in obese rats, similar to previous reports in human drug addicts. Moreover, lentivirus-mediated knockdown of striatal D2R rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuitries and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug 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.

Colocalisation of c-Fos and glucocorticoid receptor as well as of 5-HT 1A and glucocorticoid receptor immunoreactivity-expressing cells in the brain structures of low and high anxiety rats

We sought to determine the colocalisation of c-Fos (a marker of neuronal activation) and glucocorticoid receptors (GRs) as well as of 5-HT 1A and glucocorticoid receptor immunoreactivity-expressing cells (ir) in the dorsomedial prefrontal cortex (M2), dentate gyrus of the hippocampus (DG), and basolateral nucleus of the amygdala (BLA) in low and high anxiety rats (i.e., rats with duration of a freezing response in the conditioned fear test one standard error or more below or above the mean value: low responders (LR) and high responders (HR), respectively). It was found that 1.5 h after a testing session of the conditioned fear test, the LR animals had a higher activity of the cortical M2 area and DG (c-Fos), a higher expression of GRs-ir, as well as an increased number of cells co-expressing c-Fos and GRs-ir in the same brain areas. In the case of HR rats, they had similar expression of c-Fos in the BLA, but a significantly higher concentration of GRs-ir and c-Fos/GR colocalised neurons in the same amygdala nucleus. The pattern of distribution of 5-HT 1A and GR receptor-ir in LR and HR animals was similar to the c-Fos and GRs-ir expression. LR animals showed a higher density of 5-HT 1A and GRs-ir in the cortical M2 area and DG as well as an increased number of cells co-expressing 5-HT 1A and GR-ir in the same brain areas. HR rats had a significantly higher concentration of 5-HT 1A and GR-ir as well as a greater number of c-Fos/GR protein colocalised neurons in the BLA. The present data add to the arguments for the neurobiological background of differences in individual responses to aversive conditioned stimuli.

Dopamine release in response to unconditioned and conditioned aversive stimuli

Event Abstract Back to Event Dopamine release in response to unconditioned and conditioned aversive stimuli Andrew M. Young1* 1 University of Leicester, School of Psychology, United Kingdom Many studies, mainly using brain microdialysis, have reported increases in dopamine release in nucleus accumbens during presentation of aversive stimuli, such as tail pinch, mild foot shock, and restraint. Moreover, neutral stimuli such as tone, also evoke dopamine release in this brain region when they predict the onset of an aversive stimulus, by virtue of having previously been conditioned, but not when they are unconditioned [3,4]. However, the temporal and spatial resolution offered by microdialysis, even with 1 minute sampling [3], make it difficult to draw conclusions about the specific role of dopamine in these situations.Fast cyclic voltammetry (FCV) measures the oxidation of dopamine at a carbon fibre microelectrode implanted in brain tissue. Initial studies used anaesthetized animals, or brain slice preparations [2], but recent technical developments have enabled FCV to be implemented in conscious, freely moving animals [1,3]. We are therefore now able to measurement dopamine in very localized brain areas, at sub-second time resolution, in behaving animals. We have used FCV in freely moving rats to measure dopamine release during the presentation of unconditioned and conditioned aversive stimuli. These include mild footshock, a neutral low intensity tone stimulus, the same low intensity tone stimulus rendered motivationally salient, by virtue of having previously been paired with footshock in a conditioning procedure, and an intrinsically aversive (high intensity) tone. The results enable us to understand better the role of dopamine in responses to motivational and non-motivational stimuli.

The role of the dorsomedial part of the prefrontal cortex serotonergic innervation in rat responses to the aversively conditioned context: Behavioral, biochemical and immunocytochemical studies

In this study we have explored differences in animal reactivity to conditioned aversive stimuli using the conditioned fear test (a contextual fear—freezing response), in rats subjected to the selective lesion of the prefrontal cortex serotonergic innervation, and differing in their response to the acute painful stimulation, a footshock (HS – high sensitivity rats, and LS – low sensitivity rats, selected arbitrarily according to their behavior in the ‘flinch-jump’ pre-test). Local administration of serotonergic neurotoxin (5,7-dihydroxytryptamine) to the dorsomedial part of the prefrontal cortex caused a very strong, structure and neurotransmitter selective depletion of serotonin concentration. In HS rats, the serotonergic lesion significantly disinhibited rat behavior controlled by fear, enhanced c-Fos expression in the dorsomedial prefrontal area, and increased the concentration of GABA in the basolateral amygdala, measured in vivo after the testing session of the conditioned fear test. The LS animals revealed an opposite pattern of behavioral and biochemical changes after serotonergic lesion: an increase in the duration of a freezing response, and expression of c-Fos in the basolateral and central nuclei of amygdala, and a lower GABA concentration in the basolateral amygdala. In control conditions, c-Fos expression did not differ in LS and HS, naïve, not conditioned and not exposed to the test cage animals. The present study adds more arguments for the controlling role of serotonergic innervation of the dorsomedial part of the prefrontal cortex in processing emotional input by other brain centers. Moreover, it provides experimental data, which may help to better explain the anatomical and biochemical basis of differences in individual reactivity to stressful stimulation, and, possibly, to anxiolytic drugs with serotonergic or GABAergic profiles of action.

Expression of c-Fos and CRF in the brains of rats differing in the strength of a fear response

The aim of the study was to examine the neurochemical background of differences in the individual responses to conditioned aversive stimuli, using the strength of a rat conditioned freezing response (the contextual fear test), as a discriminating variable. It was shown that low responders (LR), i.e. rats with duration of a freezing response one standard error, or more, below the mean value, had a higher activity of the M2 cortical area, and the median raphe nucleus (c-Fox expression), in comparison to the high responders (HR), i.e. rats with the duration of a freezing response one standard error, or more, above the mean value. These animals had also stronger 5-HT- and CRF-related immunostaining in the M2 area, and increased concentration of GABA in the basolateral nucleus of amygdala ( in vivo microdialysis). The LR group vocalized more during test session in the aversive band, and had higher serum levels of corticosterone, examined 10 min after test session. It was shown that different natural patterns of responding to conditioned aversive stimuli are associated with different involvement of brain structures and with dissimilar neurochemical mechanisms.

Behavioral, immunocytochemical and biochemical studies in rats differing in their sensitivity to pain

The aim of the study was to further explore the anatomical and neurochemical background of differences in response to the conditioned aversive stimuli. The different patterns of behavioral coping strategies (a conditioned freezing response and ultrasonic vocalization) were analyzed in animals differing in their response to the acute painful stimulation, a foot-shock (HS: high sensitivity rats, LS: low sensitivity rats, and MS: medium sensitivity rats, according to their behavior in the flinch-jump pre-test), and correlated with plasma corticosterone levels, expression of c-Fos protein, and distribution of 5-HT innervation, in different brain structures. It was found that HS rats showed significantly more freezing behavior, whereas LS animals vocalized much more intensively. The behavior of LS group (less freezing response and stronger vocalization) was related to activation of prefrontal cortex (PFCX), increased activity of adrenal glands and stronger serotonin immunostaining in the PFCX, in comparison with HS animals. The more passive strategy of coping with the aversive event of HS group was related to increased activity of amygdalar nuclei and some areas of the hippocampus, and stronger 5-HT immunostaining in the baso-lateral nucleus of the amygdala, in comparison with LS rats. The present findings suggest that animals more vulnerable to stress might have innate deficits in the activity of brain systems controlling the hypothalamic-pituitary-adrenal axis that would normally allow them to cope with stressful situations. It appears also that response to pain may determine other patterns of emotional behavior, probably reflecting different activation thresholds of some brain structures controlling anxiety, e.g. prefrontal and secondary motor cortex.

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation (LTP) was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber B (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD.

Two definitions of punishment.

Two different definitions of punishment figure in behavior-analytic literature. In a widespread definition, advocated by Azrin and Holz (1966), punishment is defined as a procedure in which (1) certain responses have consequences, (2) those responses decrease in frequency, and (3) decrease in frequency occurs because of response-consequence relation, and not for some other reason. Keywords: punishment; theory; Skinner ********** In Science and Human Behavior, Skinner (1953) had espoused another definition of According to Skinner's definition, punishment is a procedure in which responses are followed by either (a) removal of a positive reinforcer, or (b) presentation of a negative reinforcer (or aversive stimulus). The definition requires that positive and negative reinforcers are identified through respective procedures of positive and negative reinforcement. The Azrin/Holz definition follows functional-definition pattern of reinforcement by presupposing a particular behavioral result. Thus, according to Catania (1998): and punishment are symmetrical: The former increases responding whereas latter decreases (p. 91). A similar functional definition of punishment appears in Baldwin and Baldwin (1981), Donahoe and Palmer (1994), Fantino and Logan (1979), Grant and Evans (1994), Johnston and Pennypacker (1993), Latham (1996), Leslie (1996), Martin and Pear (1996), Novak (1996), Pierce and Epling (1999), and in Rachlin (1976), just to mention a few. Although most current behavior-analytic texts seem to have adopted Azrin/Holz (1966) definition of punishment without even mentioning existence of a different one, an exception is behavior modification textbook by Martin and Pear (1996), in which Skinner's (1953) definition is briefly mentioned. A more distinct exception is Sidman's (1989) book, Coercion and its Fallout : Reinforcement differs in an important way from We define reinforcers--positive or negative--by their special effect on conduct: they increase future likelihood of actions that they follow. But we define punishment without appealing to any behavioral effect: punishment occurs whenever an action is followed either by a loss of positive or a gain of negative reinforcers. This definition says nothing about effect of a punisher on action that produces it. It does not say that punishment is opposite of reinforcement. It does not say that punishment reduces future likelihood of punished actions. (p. 39) Two Theories of Punishment Apparently, two different definitions of punishment largely coincide with two different theories of According to first theory, reinforcement and punishment are not symmetrical. In most extreme version of this view, which can be traced back to Thorndike's work in early 30's, punishment has no direct effect at all upon rate of responding. According to Thorndike (1932, p. 34), the wrong tendencies are not reduced in strength one jot or tittle by punishment. In addition to Thorndike's own experiments, early support for such a denial of effectiveness of punishment in reducing response rates (i.e., that effect of punishment is simply opposite of that of reinforcement) came from Skinner's (1938) experiments and from Estes (1944). Skinner (1938) found that when rats' lever presses were punished during a limited time period, responding was just suppressed and when punishment procedure was terminated, response rates increased such that total number of responses emitted was unaffected by Estes (1944) found that response-independent electric shocks suppressed responses about as well as response-dependent shocks. Hence, results suggested a two-factor competing response theory of punishment according to which punishment is effective only to extent that it elicits responses that are incompatible with punished response, or by producing conditioned aversive stimuli from which organism can escape only by emitting behavior which is incompatible with punished behavior. …

Processing of a simple aversive conditioned stimulus in a divided visual field paradigm: an fMRI study

A left visual hemifield advantage for the processing of negative facial expressions has been demonstrated in a variety of studies. We tested whether the same effect is found for a neutral facial expression that had acquired a negative meaning through pairing with an aversive event. Startle reflex amplitudes, skin-conductance responses (SCR), and two verbal measures of affect (negative valence and arousal) were significantly increased after pairing, but no stimulation side by pairing interaction was observed. Functional magnetic resonance imaging (fMRI) revealed a significant increase of BOLD (blood oxygen level dependent) activity in the medial prefrontal cortex (MPFC), and the right frontal opercular region (RFOP). MPFC activity was correlated with psychophysiological and verbal emotional responses across subjects and, like these responses, was independent of the stimulation side. In contrast, RFOP activity was significantly stronger during left than during right hemifield stimulation but did not correlate with psychophysiological or verbal measures of negative affect. These results suggest that emotional responses to an aversive conditioned expressively neutral face are similar in both visual hemifields. MPFC activity seems to be closely linked to the strength of these responses.

Tetrodotoxin-dependent glutamate release in the rat nucleus accumbens during concurrent presentation of appetitive and conditioned aversive stimuli

In vivo microdialysis combined with a high-performance liquid chromatography was used to monitor extracellular glutamate (GLU) levels in the nucleus accumbens (N.Acc) of Sprague-Dawley rats during their behavioral responses to the concurrent presentation of appetitive and conditioned aversive stimuli. The presentation of a highly palatable diet followed by a tone previously paired with footshock to rats trained to take a pellet of the diet under these experimental conditions resulted in a marked and short lasting increase in extracellular glutamate, whereas the tone alone had no effect. A similar increase of the glutamate release was observed during the presentation of a piece of rubber instead of the diet. In both cases, the increase in extracellular glutamate was completely prevented by intra-accumbal infusions through the dialysis probe of 1 μM tetrodotoxin (a voltage-dependent Na + channel blocker), whereas (S)-4-carboxyphenylglycine (a cystine/glutamate exchange blocker, 5 μM) had no effect. The data obtained suggest that behavioral responses to unpredicted change in motivational value of expected reward appear to be associated with an increase of the extracellular glutamate level in the nucleus accumbens, and impulse-dependent synaptic release, rather than non-vesicular glutamate release via cystine/glutamate exchange, is responsible for this phenomenon.

Drug seeking becomes compulsive after prolonged cocaine self-administration.

Compulsive drug use in the face of adverse consequences is a hallmark feature of addiction, yet there is little preclinical evidence demonstrating the actual progression from casual to compulsive drug use. Presentation of an aversive conditioned stimulus suppressed drug seeking in rats with limited cocaine self-administration experience, but no longer did so after an extended cocaine-taking history. In contrast, after equivalent extended sucrose experience, sucrose seeking was still suppressed by an aversive conditioned stimulus. Persistent cocaine seeking in the presence of signals of environmental adversity after a prolonged cocaine-taking history was not due to impaired fear conditioning, nor to an increase in the incentive value of cocaine, and may reflect the establishment of compulsive behavior.

Increased extracellular dopamine in nucleus accumbens in response to unconditioned and conditioned aversive stimuli: studies using 1 min microdialysis in rats

Previous microdialysis studies measuring extracellular dopamine levels in response to unconditioned and conditioned aversive stimuli have used relatively long (e.g. 10 min) sample durations, such that more than one stimulus event occurred within a single dialysis sample. The present study used 1 min dialysate sampling to measure changes in dopamine levels in response to individual stimulus presentations. The changes evoked by mild footshock showed an initial enhancement from the first to the second presentation, after which there was a steady decline in the response over subsequent presentations. Compared to the responses to footshock alone, when the footshock was paired with an unfamiliar tone, there was no change in the response to the first stimulus presentation, but a significant augmentation of responses during subsequent presentations, giving weight to the view that dopamine is not involved in the learning per se, but rather in the processing of learned information. Whilst an unfamiliar tone had no measurable effect on extracellular dopamine levels, the same tone which had previously been paired with footshock evoked a significant increase in dopamine during the tone presentation, indicating that it is the aversive nature of the stimulus onset rather than the ‘rewarding’ nature of its offset which increases extracellular dopamine.

Amygdala c-Fos induction corresponds to unconditioned and conditioned aversive stimuli but not to freezing

These experiments examined the relationship between freezing and c-Fos expression in the amygdala. In Experiment 1 freezing was elevated during a period immediately following shock in rats that remained in the shock context, but not in rats that were moved to a different, neutral context. The two groups showed equally elevated c-Fos levels in both the central (CeA) and lateral (LA) nuclei. In Experiment 2 rats were shocked in one compartment (paired) and not shocked in another, distinct compartment (unpaired). Rats re-exposed to the paired compartment 24 h later froze more than rats exposed to the unpaired compartment, and rats in both groups froze more than un-shocked rats. c-Fos protein expression in CeA, LA and basolateral (BLA) nucleus was elevated in the rats exposed to the paired compartment but not in rats exposed to the unpaired compartment. Thus, c-Fos expression was induced by exposure to both unconditioned and conditioned stimuli, although it is unclear if the same cell population was activated in both cases. Neither case of c-Fos expression coincided with the occurrence of freezing. c-Fos expression may represent neural activity in LA and CeA produced by exposure to unconditioned cues and activity in BLA, LA and CeA produced by conditioned cues. This activity may contribute to an aversive affective state (or “fear”). Behaviors promoted by this state, such as freezing, may be mediated in other brain areas, or by other neurons in the amygdala.

Nucleus accumbens dopamine and learned fear revisited: a review and some new findings

A role for the nucleus accumbens (NAcc) and its dopamine (DA) innervation in fear and fear learning is supported by a large body of evidence, which has challenged the view that the NAcc is solely involved in mediating appetitive processes. Unfortunately, due to conflicting findings in the aversive conditioning literature the role of the NAcc in aversive conditioning remains unclear. This review focuses on the results of recent in vivo microdialysis studies that have examined the release of NAcc DA during Pavlovian aversive conditioning. In addition, we present additional new findings, which re-examine the involvement of NAcc DA in aversive conditioning. DA release was measured in the NAcc core using in vivo microdialysis during discrete cue Pavlovian aversive conditioning in four experiments. In all cases no change in DA levels was observed either during training or in response to the CS presentations despite robust behavioural evidence of discrete cue Pavlovian aversive conditioning. These findings contrast with some previous studies that show that primary and conditioned aversive stimuli increase DA release in the NAcc. We suggest that the inconsistencies in the literature might be due to procedural differences in the measurement of aversive conditioning, and the precise location of the probe in the NAcc region. Hence, rather than discount an involvement of NAcc DA in affective processes, we propose that functionally dissociable sub-regions of the NAcc may contribute to different aspects of Pavlovian aversive learning.

Behavioral expression of learned fear in rats is appropriate to their age at training, not their age at testing.

Recent research has shown that learned fear emerges in a response-specific sequence. For example, an odor conditioned stimulus (CS) previously paired with shock elicits behavioral expressions of fear like avoidance at a younger age than it elicits other behavioral expressions of fear like potentiation of the startle response (Richardson, Paxinos, & Lee, 2000). In the present study, the question of whether learned fear is expressed in a manner appropriate to the animal's age at training or its age at testing was explored in three experiments, all using a within-subjects design. The results suggest that learned fear is expressed in a manner appropriate to the rat's age at training, not its age at testing. The Discussion section focuses on the implications of these findings for (1) the developmental analysis of memory and (2) the idea that an aversive CS elicits a central state of fear.