Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “fear conditioning”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2004

Hippocampus and Pavlovian fear conditioning in rats: muscimol infusions into the ventral, but not dorsal, hippocampus impair the acquisition of conditional freezing to an auditory conditional stimulus.

The authors compared the effects of pharmacological inactivation of the dorsal hippocampus (DH) or ventral hippocampus (VH) on Pavlovian fear conditioning in rats. Freezing behavior served as the measure of fear. Pretraining infusions of muscimol, a GABAA receptor agonist, into the VH disrupted auditory, but not contextual, fear conditioning; DH infusions did not affect fear conditioning. Pretesting inactivation of the VH or DH did not affect the expression of conditional freezing. Pretraining electrolytic lesions of the VH reproduced the effects of muscimol infusions, whereas posttraining VH lesions disrupted both auditory and contextual freezing. Hence, neurons in the VH are importantly involved in the acquisition of auditory fear conditioning and the expression of auditory and contextual fear under some conditions.

Acoustic Stimulation↗
PubMed1999

Functional inactivation of the amygdala before but not after auditory fear conditioning prevents memory formation.

Two competing theories predict different effects on memory consolidation when the amygdala is inactivated after fear conditioning. One theory, based on studies using inhibitory avoidance training, proposes that the amygdala modulates the strength of fear learning, and post-training amygdala manipulations interfere with memory consolidation. The other, based on studies using Pavlovian fear conditioning, hypothesizes that fear learning occurs in the amygdala, and post-training manipulations after acquisition will not affect memory consolidation. We infused the GABAA agonist muscimol (4.4 nmol/side) or vehicle into lateral and basal amygdala (LBA) of rats either before or immediately after tone-foot shock Pavlovian fear conditioning. Pre-training infusions eliminated acquisition, whereas post-training infusions had no effect. These findings indicate that synaptic activity in LBA is necessary during learning, but that amygdala inactivation directly after training does not affect memory consolidation. Results suggest that essential aspects of plasticity underlying auditory fear conditioning take place within LBA during learning.

Acoustic Stimulation↗
PubMed1997

Quantitative trait locus analysis of contextual fear conditioning in mice.

Family, twin and adoption studies provide evidence for a substantial genetic component underlying individual differences in general intelligence, specific cognitive abilities and susceptibility to psychopathologies related to fear-inducing events. Contextual fear conditioning, which is highly conserved across species, can serve as a model for elucidating genes that regulate individual differences in learning and emotion. In fear conditioning, an initially neutral stimulus, such as a tone or a particular environment (context), elicits a fear response after it has been paired with an aversive stimulus, such as shock. Two neural circuits have been implicated in fear conditioning. The fear component is regulated by amygdaloid pathways, while the contextual component is, at least in part, dependent on the hippocampus. C57BL/6J (B6) and DBA/2J (D2) mice differ in several types of complex learning. including contextual fear conditioning. A quantitative trait locus (QTL) analysis of contextual fear conditioning was performed in a B6/D2 F2 intercross population. Two QTLs for contextual conditioning (lod score > 4.3) were identified on chromosomes 10 and 16. QTLs for conditioning to the auditory cue (lod score > 4.3) were localized to chromosomes 1 and 10. Suggestive QTLs (lod score = 2.8-4.1) for contextual conditioning were detected on chromosomes 1, 2 and 3.

Animals↗
PubMedDate not supplied

[Citrulline extracellular level in the nucleus accumbens during acquisition and extinction of classical conditioned fear response with pain reinforcement].

By means of in vivo microdialysis combined with HPLC analysis, we have shown that extracellular levels of citrulline (NO co-product) and arginine (NO precursor) increase in the rat n. accumbens during acquisition and expression of a classical fear response. The conditioned rise of citrulline and arginine levels gradually decreased in the course of extinction. The renewal of the response produced an increase in extracellular citrulline and arginine levels. These data suggest that the acquisition of conditioned fear response causes an increase in NO production in the n. accumbens that weakens during the extinction and is restored during the reinstatement of the response.

Animals↗
PubMed1998

Testicular hormones do not regulate sexually dimorphic Pavlovian fear conditioning or perforant-path long-term potentiation in adult male rats.

We recently reported that Pavlovian fear conditioning and hippocampal perforant-path long-term potentiation (LTP) are sexually dimorphic in rats. Males show greater contextual fear conditioning, which depends on the hippocampus, as well as greater hippocampal LTP. In order to examine the role of circulating gonadal hormones in adult male rats, animals were castrated in two experiments, and Pavlovian fear conditioning and in vivo perforant-path LTP were examined. It was found that sexually-dimorphic LTP and fear conditioning are not regulated by the activational effects of testicular hormones in adult male rats. That is, in every respect, castrated male rats were similar to intact male rats in Pavlovian fear conditioning and hippocampal LTP. It is likely that sexual dimorphism in this system is established earlier in development by the organizational effects of gonadal hormones.

Animals↗
PubMed1992

One-trial backward excitatory fear conditioning transfers across contexts.

One path to human phobia may be one-trial backward fear conditioning. Human phobias transfer readily across contexts. However, animal studies of one-trial backward fear conditioning have yet to demonstrate such transfer. The present study sought to do so. It used a lick-suppression procedure with 84 naive male albino rats. Two conditioning contexts, designated O and V, were crossed factorially with two test contexts, O and V. Within each cell of the factorial design, rats received in the conditioning context either a single 12 sec tone backward paired with a single 4 sec 1 mA shock or the same tone explicitly unpaired with shock. Fear of context and fear of tone were subsequently assessed in terms of the suppression of licking that they evoked. Test results suggested that (1) the rats discriminated between contexts O and V, and (2) despite such discrimination, one-trial backward fear conditioning transferred across the two contexts. The results enhance the plausibility of one-trial backward fear conditioning as a source of human phobia.

Animals↗
PubMed1992

Bilateral destruction of neocortical and perirhinal projection targets of the acoustic thalamus does not disrupt auditory fear conditioning.

The present study examined whether complete bilateral destruction of auditory cortex would interfere with auditory fear conditioning in rats. Complete destruction of auditory cortex required lesions of temporal neocortical and perirhinal periallocortical areas. Fear conditioning was assessed by measuring freezing and arterial pressure responses elicited by an acoustic stimulus after pairing with footshock. Animals with complete bilateral lesions of auditory cortex showed conditioned arterial pressure and freezing responses comparable to those of unoperated controls. In contrast, bilateral destruction of the acoustic thalamus interfered with the conditioning of both responses. These results demonstrate that the auditory cortex is not required for the conditioning of fear responses to simple acoustic stimuli and add to the growing body of evidence that fear conditioning can be mediated by subcortical (amygdaloid) projections of the acoustic thalamus.

Acoustic Stimulation↗
PubMed2006

Immediate shock deficit in fear conditioning: effects of shock manipulations.

Pavlovian contextual fear conditioning occurs when an aversive unconditional stimulus (US), such as a footshock, is presented to a rat shortly after it is placed in an experimental context. Contextual fear conditioning does not occur when the shock is presented immediately upon placement of the rat in the novel chamber. In the present study, the authors report that increasing either the number of immediate shock sessions (Experiment 1) or the immediate shock duration (Experiment 2) did not reverse this deficit. However, immediate shock seems to sensitize subsequent context conditioning (Experiment 3). These findings suggest that the associative deficit produced by immediate shock is not related to the rat's ability to process the footshock US.

Animals↗
PubMed1998

[Suppression of conditioned fear by administration of CCKB receptor antagonist PD135158].

The aim of this study is to determine whether or not CCKB receptor antagonist PD135158 suppresses conditioned fear. Rats were individually subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. PD135158 or the vehicle was administered 30 min before placing the rats in the shock chamber again. The rats were observed for 5 min without receiving shock. The administration of PD135158 30 min before conditioned-fear stress significantly reduced freezing behavior. PD135158 blocked the expression of conditioned fear. PD135158 was again administered 30 min before footshock. Then, the rats were individually subjected to 30 min of inescapable electric footshock in the shock chamber. Twenty-four hours after receiving footshock, the rats were again placed in the shock chamber and observed for 5 min without shock administration. The administration of PD135158 30 min before footshock significantly reduced conditioned freezing. PD135158 blocked the anxiety of conditioned fear. PD135158 blocked not only the anxiety, but also the expression of conditioned fear. These results suggest that CCKB receptor might play an important role in conditioned-fear stress. They indicate that CCKB receptor is related to anxiety.

Animals↗
PubMed2006

Fear conditioning and extinction: influence of sex and menstrual cycle in healthy humans.

Although sex differences have been demonstrated in behavioral paradigms of fear conditioning, the findings have been inconsistent, and fear extinction has been little studied. The present study investigated the influence of sex and menstrual cycle phase on the recall of fear extinction. Three groups of healthy adult participants were studied: women at 2 different phases of the menstrual cycle (early follicular [early cycle] and late follicular [midcycle]) and men. Participants underwent a 2-day fear conditioning and extinction protocol. The paradigm entailed habituation, fear conditioning, and extinction learning on Day 1 and extinction recall and fear renewal on Day 2. Skin conductance served as the dependent variable. During fear acquisition on Day 1, men showed significantly larger conditioned responses relative to women; early cycle and midcycle women did not differ. No significant group differences were found during extinction learning. On Day 2, men and early cycle women expressed greater extinction memory than midcycle women. These data confirm sex differences in conditioned fear acquisition and suggest that midcycle hormones attenuate extinction recall.

Adult↗
PubMedDate not supplied

Application of Pavlovian higher-order conditioning to the analysis of the neural substrates of fear conditioning.

In Pavlovian first-order conditioning, a conditioned response is acquired by pairing a neutral stimulus (S1) with a stimulus that has innate motivational value. In higher-order conditioning, a neutral stimulus (S2) is paired with S1 either after (second-order conditioning) or before (sensory preconditioning) first-order conditioning has been acquired. Thus, in higher-order conditioning the motivational value of the reinforcer is acquired rather than innate. This review describes some of the potential uses of higher-order conditioning in investigating the neural substrates of fearful memories. First, because in second-order fear conditioning S2 is not paired directly with a painful stimulus, any effect of a treatment on the acquisition of fear cannot be attributed to the treatment's possible effects on transmission of nociceptive information. Second, higher-order conditioning provides opportunities for analyzing where and how different types of events, or different aspects of the same events, are represented in the brain.

Animals↗
PubMed1999

Discriminative fear conditioning to context expressed by multiple measures of fear in the rat.

There has been a renewed interest in the neural basis of fear conditioning to context. These current approaches are accompanied by some limitations including the use of short testing windows, non-discriminative paradigms, and unitary fear response assessment. In an attempt to circumvent these limitations, a discriminative context procedure assessing multiple response measures of fear was used in the present study. Conditioning consisted of three training sessions and each session consisted of 2 days. On day one, the animals were placed in the paired context and received three foot shocks. On the other day, they were placed in the unpaired chamber in the absence of any aversive event. Animals were tested after each training session and the response measures of fear recorded included: preference, freezing, heart rate, ultrasonic vocalizations, defecation, body temperature, urination and locomotion. The results suggest that behavioral, as well as physiological changes evoked by fearful stimuli become associated with the context in which the aversive event occurred. In general these findings also suggest that there are different learning parameters for the measures of fear examined in this paradigm.

Animals↗
PubMed2004

Effects of the beta-blocker propranolol on cued and contextual fear conditioning in humans.

RATIONALE: Beta-adrenergic receptors are involved in the consolidation of emotional memories. Yet, a number of studies using Pavlovian cued fear conditioning have been unable to demonstrate an effect of beta-adrenergic blockade on acquisition or retention of fear conditioning. Evidence for the involvement of beta-adrenergic receptors in emotional memories comes mostly from studies using fear inhibitory avoidance in rodents. It is possible that fear inhibitory avoidance is more akin to contextual conditioning than to cued fear conditioning, suggesting that context conditioning may be disrupted by beta-adrenergic blockade. OBJECTIVE: This study investigated the effects of the beta-adrenergic blocker propranolol on cued and contextual fear conditioning in humans. METHODS: Subjects were given either placebo (n=15) or 40 mg propranolol (n=15) prior to differential cued conditioning. A week later, they were tested for retention of context and cued fear conditioning using physiological (startle reflex and electrodermal activity) and subjective measures of emotional arousal. RESULTS: The results were consistent with the hypothesis. The skin conductance level (SCL) and the subjective measure of arousal suggested reduced emotional arousal upon returning to the conditioning context in the propranolol group, compared to the placebo group. The acquisition and retention of cued fear conditioning were not affected by propranolol. CONCLUSIONS: These results suggest that beta-adrenergic receptors are involved in contextual fear conditioning.

Adrenergic beta-Antagonists↗
PubMed2003

Prior exposure to a single stress session facilitates subsequent contextual fear conditioning in rats. Evidence for a role of corticosterone.

Previous studies showed that exposure of rats to chronic restraint stress for 21 days enhances subsequent contextual fear conditioning. Since recent evidence suggest that this effect is not dependent on stress-induced neurodegenerative processes, but to elevated training-elicited glucocorticoid release in chronically stressed animals, we aimed to explore here whether a single exposure to restraint stress, which is not expected to induce neuronal damage, would also affect contextual fear conditioning. We also questioned whether post-training corticosterone levels might be associated with any potential effect of stress on fear conditioning. Adult male Wistar rats were exposed to acute restraint stress for 2 h and, two days later, trained in the contextual fear conditioning task, under training conditions involving either moderate (0.4 mA shock) or high (1 mA shock) stress levels. The results showed that acute stress enhanced conditioned freezing at both training conditions, although data from the 1 mA shock intensity experiment only approached significance. Stressed animals were shown to display higher post-training corticosterone levels. Furthermore, the facilitating effect of prior stress was not evident when animals were trained in the hippocampal-independent auditory-cued conditioning task. Therefore, these findings support the idea that stress experiences preceding exposure to new types of stressors facilitate the development of contextual fear conditioning. They also indicate that not only repeated, but also a single exposure to aversive stimulation is sufficient to facilitate context-dependent fear conditioning, and suggest that increased glucocorticoid release at training might be implicated in the mechanisms mediating the memory facilitating effects induced by prior stress experiences.

Acoustic Stimulation↗
PubMedDate not supplied

Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear.

Recent studies using lesion, infusion, and unit-recording techniques suggest that the infralimbic (IL) subregion of medial prefrontal cortex (mPFC) is necessary for the inhibition of conditioned fear following extinction. Brief microstimulation of IL paired with conditioned tones, designed to mimic neuronal tone responses, reduces the expression of conditioned fear to the tone. In the present study we used microstimulation to investigate the role of additional mPFC subregions: the prelimbic (PL), dorsal anterior cingulate (ACd), and medial precentral (PrCm) cortices in the expression and extinction of conditioned fear. These are tone-responsive areas that have been implicated in both acquisition and extinction of conditioned fear. In contrast to IL, microstimulation of PL increased the expression of conditioned fear and prevented extinction. Microstimulation of ACd and PrCm had no effect. Under low-footshock conditions (to avoid ceiling levels of freezing), microstimulation of PL and IL had opposite effects, respectively increasing and decreasing freezing to the conditioned tone. We suggest that PL excites amygdala output and IL inhibits amygdala output, providing a mechanism for bidirectional modulation of fear expression.

Animals↗
PubMed1997

Second-order fear conditioning prevented by blocking NMDA receptors in amygdala.

Antagonists of NMDA (N-methyl-D-aspartate)-type glutamate receptors disrupt several forms of learning. Although this might indicate that NMDA-receptor-mediated processes are critical for synaptic plasticity, there may be other mechanisms by which NMDA-receptor antagonism could interfere with learning. For instance, fear conditioning would be blocked by microinfusion of the NMDA-receptor antagonist AP5 (D,L-2-amino-5-phosphonovalerate) into the basolateral amygdala if AP5 inhibited routine synaptic transmission, thereby reducing the ability of stimuli to activate amygdala neurons. In second-order fear conditioning, the reinforcer is a fear-eliciting conditioned stimulus rather than an unconditioned stimulus. Expression of conditioned fear is amygdala-dependent and so provides a behavioural assessment of the ability of the reinforcer to activate amygdala neurons in the presence of AP5. We report here that intra-amygdala AP5 actually enhances expression of conditioned fear to the conditioned stimulus that provides the reinforcement signal for second-order conditioning. Nevertheless, acquisition of second-order fear conditioning is completely blocked. Our findings strongly support the view that NMDA receptors are critically involved in synaptic plasticity.

2-Amino-5-phosphonovalerate↗
PubMed2004

Unconditioned stimulus pathways to the amygdala: effects of posterior thalamic and cortical lesions on fear conditioning.

Plasticity in the lateral nucleus of the amygdala is thought to be critical for the acquisition of Pavlovian fear conditioning. The pathways that transmit auditory conditioned stimulus information originate in auditory processing regions of the thalamus and cortex, but the pathways mediating transmission of unconditioned stimuli to the amygdala are poorly understood. Recent studies suggest that somatosensory (footshock) unconditioned stimulus information is also relayed in parallel to the lateral nucleus of the amygdala from the thalamus (the posterior intralaminar thalamic complex, PIT) and the cortex (parietal insular cortex). In the present study we reexamined this issue. Our results showed that bilateral electrolytic lesions of the PIT alone blocked fear conditioning, whereas bilateral excitotoxic PIT lesions had no effect. These electrolytic PIT lesions did not affect fear conditioning using a loud noise as unconditioned stimulus, defining the effects of PIT lesions as a disruption of somatosensory as opposed to auditory processing. Finally, we performed combined bilateral excitotoxic lesions of the PIT nuclei and electrolytic lesions of the parietal insular cortex. These, like excitotoxic lesions of PIT alone, had no effect on the acquisition of fear conditioning. Thus, somatosensory regions of the thalamus and cortex may well be important routes of unconditioned stimulus transmission to the amygdala in fear conditioning, but information about the unconditioned somatosensory stimulus is also transmitted from other sources that send fibers through, but do not form essential synapses in, the thalamus en route to the amygdala.

Amygdala↗
PubMed2003

Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning.

The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days post-training. However, this treatment failed to influence conditioning for this task when injected 2 days pre-training. Additional experiments showed that C3d did not influence the emotional or locomotor behaviour of the animals, when tested in the open field task. Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the cognitive impact induced by exposure to intensive stress experiences.

Animals↗