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 523 records · Page 29Linked to original sources
PubMed2005

Estrogen facilitates fear conditioning and increases corticotropin-releasing hormone mRNA expression in the central amygdala in female mice.

Estrogens exert important actions on fear and anxiety-like behavior both in humans and non-human animals. Currently, the mechanisms underlying estrogenic modulation of fear are not known. However, evidence suggests that estrogens may exert their influence on fear within the amygdala. The purpose of the present study was to examine effects of estrogen on fear conditioning. Specifically, the present study examined whether long-term estrogen treatment in ovariectomized female mice via Silastic capsule implantation would facilitate both contextual and cued fear conditioning. In a separate set of experiments, we then examined whether estrogen treatment in ovariectomized female mice would modulate corticotropin-releasing hormone (CRH) gene expression within the amygdala. Long-term estrogen treatment facilitated both contextual and cued fear. Ovariectomized mice treated with estrogen froze significantly more to a context as well as to a discrete auditory cue. In addition, estrogen treatment significantly increased CRH mRNA expression within the central nucleus of the amygdala as measured by in situ hybridization and quantitative PCR. These data raise the possibility that estrogens could influence fear responses in females through their actions in the amygdala.

Amygdala↗
PubMed1997

Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala.

Single neurons were recorded in freely behaving rats during fear conditioning from areas of auditory cortex that project to the lateral nucleus of the amygdala (LA). The latency and rate of conditioning and extinction were analyzed, and the results were compared to previous recordings from LA itself. Auditory cortex neurons took more trials to learn, and they responded more slowly than LA neurons within trials. Short-latency plasticity in LA, therefore, reflects inputs from the auditory thalamus rather than the auditory cortex. Unlike LA cells, some auditory cortex cells showed late conditioned responses that seemed to anticipate the unconditioned stimulus, while others showed extinction-resistant memory storage. Thus, rapid conditioning of fear responses to potentially dangerous stimuli depends on plasticity in the amygdala, while cortical areas may be particularly involved in higher cognitive (mnemonic and attentional) processing of fear experiences.

Acoustic Stimulation↗
PubMed1999

Roles of 5-HT3 and opioid receptors in the ethanol-induced place preference in rats exposed to conditioned fear stress.

The effect of the selective 5-HT3 receptor antagonist ondansetron on the ethanol-induced place preference in rats exposed to conditioned fear stress, which stimulates the release of endogenous opioid peptides (beta-endorphin and enkephalins), was investigated using the conditioned place preference paradigm. In addition, we also examined the effect of ondansetron on the ethanol-induced place preference enhanced by the administration of mu- and delta-opioid receptor agonists (exogenous opioids). The administration of ethanol (300 mg/kg, i.p.) induced a significant place preference in rats exposed to conditioned fear stress. Pretreatment with ondansetron (0.01 and 0.1 mg/kg, s.c.) effectively attenuated this ethanol-induced place preference. When the mu-opioid receptor agonist morphine (0.1 mg/kg, s.c.) or the selective delta-opioid receptor agonist 2-methyl-4a(alpha)-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a(alpha)-octah ydroquinolino [2,3,3-g] isoquinoline (TAN-67; 20 mg/kg, s.c.) was administered in combination with 75 mg/kg ethanol (which tended to produce a place preference), the ethanol-induced place preference was significantly enhanced. The selective mu-opioid receptor antagonist beta-funaltrexamine at a dose of 10 mg/kg significantly attenuated the enhancement of the ethanol-induced place preference produced by morphine. Ondansetron (0.1 mg/kg, s.c.) also significantly attenuated the enhancement of the ethanol-induced place preference produced by morphine. Furthermore, the selective delta-opioid receptor antagonist naltrindole at a dose of 3 mg/kg significantly attenuated the enhancement of the ethanol-induced place preference produced by TAN-67. Ondansetron (0.1 mg/kg, s.c.) slightly, but significantly, attenuated the enhancement of the ethanol-induced place preference produced by TAN-67. These results suggest that 5-HT3 receptors may be involved in the rewarding mechanism of ethanol under psychological stress, and may play an important role in the rewarding effect of ethanol through the activation of mu- and delta-opioid receptors.

Animals↗
PubMed1997

Odor-guided fear conditioning in rats: 1. Acquisition, retention, and latent inhibition.

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)-unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS-US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more at any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning.

Animals↗
PubMed2002

Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: context discrimination and the effects of retention interval.

Context discrimination and time course studies of contextual fear conditioning revealed strain differences between C57BL/6J (B6) and DBA/2J (D2) mice. Both strains discriminated contexts, but D2 mice exhibited less freezing in a shock-paired context. The strains did not differ immediately, or at 1 and 3 hr after contextual fear conditioning training. D2 mice showed less freezing at 15 min, 30 min, and 24 hr after training. B6 mice exhibited exaggerated generalized freezing and poor discrimination between the context and altered context 7-30 days after training. The acoustic startle response in B6 mice was also enhanced at 14 days after training. D2 mice did not show this pattern of generalized freezing. B6, but not D2, mice retained contextual memories for at least 60 days.

Animals↗
PubMed2002

Post-training excitotoxic lesions of the dorsal hippocampus attenuate forward trace, backward trace, and delay fear conditioning in a temporally specific manner.

The present study sought to determine whether post-training excitotoxic lesions of the dorsal hippocampus would disrupt retention of fear conditioned using a trace procedure. Rats were trained using one of six procedures. Forward trace conditioning consisted of 10 trials in which a 16-s tone conditional stimulus (CS) was followed by a 28-s stimulus-free trace interval and then a mild footshock unconditional stimulus (US). We used two forms of delay conditioning where the tone and footshock co-terminated. Short delay used a 16-s tone and long delay used a 46-s tone. Backward trace conditioning was the same as forward trace, except that the order of the CS and US was reversed. CS-only and US-only were similar to forward trace except that the footshock or tone, respectively, was eliminated. One day later, animals received either an N-methyl-D-aspartate (NMDA)-induced lesion of the dorsal hippocampus or sham surgery. One week later, the rats were tested for freezing to the tone in a novel context. The next day, they were tested for freezing to the original training context. Hippocampal lesioned trace conditioned rats showed significantly less freezing during the tone compared with their sham lesioned controls. The lesion did not affect freezing during the tone in delay conditioning, nor in the other training conditions. During the 1-min period after tone offset, there was a trend in all hippocampal lesioned animals toward a deficit in freezing, compared with their corresponding sham lesioned controls, although only short delay, forward and backward trace groups showed a significant deficit. Hippocampal lesions also attenuated contextual conditioning. Thus, the hippocampus is critical for the consolidation and/or expression of a trace fear conditioned stimulus.

Animals↗
PubMed2004

Neural substrates mediating human delay and trace fear conditioning.

Previous functional magnetic resonance imaging (fMRI) studies with human subjects have explored the neural substrates involved in forming associations in Pavlovian fear conditioning. Most of these studies used delay procedures, in which the conditioned stimulus (CS) and unconditioned stimulus (UCS) coterminate. Less is known about brain regions that support trace conditioning, a procedure in which an interval of time (trace interval) elapses between CS termination and UCS onset. Previous work suggests significant overlap in the neural circuitry supporting delay and trace fear conditioning, although trace conditioning requires recruitment of additional brain regions. In the present event-related fMRI study, skin conductance and continuous measures of UCS expectancy were recorded concurrently with whole-brain blood oxygenation level-dependent (BOLD) imaging during direct comparison of delay and trace discrimination learning. Significant activation was observed within the visual cortex for all CSs. Anterior cingulate and medial thalamic activity reflected associative learning common to both delay and trace procedures. Activations within the supplementary motor area (SMA), frontal operculum, middle frontal gyri, and inferior parietal lobule were specifically associated with trace interval processing. The hippocampus displayed BOLD signal increases early in training during all conditions; however, differences were observed in hippocampal response magnitude related to the accuracy of predicting UCS presentations. These results demonstrate overlapping patterns of activation within the anterior cingulate, medial thalamus, and visual cortex during delay and trace procedures, with additional recruitment of the hippocampus, SMA, frontal operculum, middle frontal gyrus, and inferior parietal lobule during trace conditioning. These data suggest that the hippocampus codes temporal information during trace conditioning, whereas brain regions supporting working memory processes maintain the CS-UCS representation during the trace interval.

Adolescent↗
PubMed2002

Long-term potentiation as a substrate for memory: evidence from studies of amygdaloid plasticity and Pavlovian fear conditioning.

Recent reports have raised concerns about the ability of long-term potentiation (LTP) to account for associative learning and memory. In this paper, we review the many mechanistic similarities between one form of associative learning, Pavlovian fear conditioning, and amygdaloid LTP. We then address many of the criticisms levied against LTP within the framework of fear conditioning. We believe that many of the apparent discrepancies between LTP and behavior can be generally accounted for by a failure to appreciate that learned behavior is supported by multiple synapses in an extensive network of brain structures. We conclude that LTP remains a viable substrate for memory.

Amygdala↗
PubMed2003

Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression.

Cleavage of the cyclin-dependent kinase 5 activator p35 generates the protein fragment p25, which accumulates in the forebrain of patients with Alzheimer's disease. Although p25 expression has been suggested to affect learning and memory, this hypothesis has not been tested to date. To investigate the role of p25 in hippocampus-dependent learning and memory we have generated transgenic mice expressing p25 preferentially in postnatal forebrain. p25 expression was highest in hippocampus where it averaged approximately 33% of endogenous p35 expression. This low level of p25 expression did not seem to result in hyperphosphorylation of tau, but increased the phosphorylation of neurofilament M and enhanced the expression of tau protein. These molecular changes did not correlate with neurodegeneration or motor abnormalities. In the Morris water maze the p25 mutants were normal in learning an initial platform location, but surprisingly reversal learning was improved when the platform position was changed. The p25 mutants were normal in contextual fear conditioning. However, when trained with a tone presentation the mutants showed reduced contextual conditioning and enhanced tone fear conditioning. We conclude that low p25 expression has pleiotropic effects on learning and memory. As p25 expression can improve learning and memory, p25 formation could be a compensatory mechanism for learning and memory deficits in Alzheimer's disease.

Alzheimer Disease↗
PubMed2003

Anterograde amnesia for Pavlovian fear conditioning and the role of one-trial overshadowing: effects of preconditioning exposures to morphine in the rat.

Four experiments studied anterograde deficits in Pavlovian fear conditioning following prolonged exposure to the mu-opioid receptor agonist morphine. Injections of morphine produced temporally graded anterograde amnesia characterized by deficits in contextual and conditioned-stimulus (CS) conditioning 1 or 7 days and selective impairment in CS conditioning 21 days after last injection. This anterograde deficit in conditioning did not recover across a retention interval, was absent when rats were tested immediately after conditioning, and required the presence of an auditory CS. These results suggest that anterograde deficits in Pavlovian fear conditioning emerged from differences in susceptibility to 1-trial overshadowing of context by CS.

Acoustic Stimulation↗
PubMed2000

Auditory fear conditioning increases CS-elicited spike firing in lateral amygdala neurons even after extensive overtraining.

We examined the influence of extensive overtraining (75 trials) of auditory fear conditioning on the expression of conditional stimulus (CS)-elicited spike firing in lateral amygdala (LA) neurons. Single units were recorded from chronic multichannel electrodes implanted in the LA of conscious and freely moving rats. In sequential training sessions, the rats received either five or 70 fear conditioning trials, which consisted of a white-noise CS and a coterminating footshock unconditional stimulus (US). Unpaired (sensitization) controls received the same number of trials, but the CS and US were explicitly unpaired. Paired CS-US presentations yielded robust increases in CS-elicited spike firing in LA neurons after both five and 70 conditioning trials, and the magnitude of the spike firing increases was correlated with the expression of conditional freezing to the CS. After 75 training trials, maximal conditioning-related increases in LA firing were exhibited within 20 ms of CS onset, indicating that this increase is mediated by direct thalamo-amygdala projections. There was no significant increase in CS-elicited spike firing or freezing behaviour in the unpaired group. These results complement amygdala lesion studies [e.g. Maren, S. (1999a) J. Neurosci., 19, 8696-8703] and support the view that the basolateral complex of the amygdala is involved in the encoding and storage of fear memories even after extensive overtraining.

Acoustic Stimulation↗
PubMed1990

Examination of a backchaining/counterconditioning process during the extinction of conditioned fear.

Two experiments using rat subjects are reported which attempt to delineate the theoretical mechanisms involved in exposure/extinction procedures that are used to eliminate conditioned fear. In Experiment 1, a within-subjects design was employed to study the temporal course of the extinction process by examining the relationship among three separate measures of classically conditioned fear--suppression of an ongoing, operant behavior during the nonreinforced fear-eliciting CS presentation, the time to the first response during this CS presentation, and the time to recover responding following termination of the CS. The results indicated a temporal relationship among these measures, both within and across nonreinforced CS trials, which were considered to reflect a backchaining of a fear-antagonistic response during extinction, and provided an empirical demonstration of an extinction process consistent with Denny's (Behaviour Therapy and Experimental Psychiatry, 7, 315-321, 1976) elicitation/backchaining explanation of extinction. Experiment 2 attempted to manipulate the course of extinction and the temporal relationship among these three fear measures through the paired presentations of the fear CS with a palatable substance (maltose). This procedure produced greater extinction apparently by facilitating the backchaining process. These results are discussed with implications for exposure-based therapies.

Arousal↗
PubMed2001

Fast spiking and regular spiking neural correlates of fear conditioning in the medial prefrontal cortex of the rat.

In order to investigate whether and how medial prefrontal cortex (mPFC) of the rat is involved in processing of information related to fear conditioning, we recorded from single units in the prelimbic and infralimbic cortex of fear-conditioned rats in response to an explicit conditional stimulus (CS; an auditory tone) or contextual cues (conditioning box). The majority of units changed their activities significantly in response to the CS in a delay or trace conditioning paradigm. Both transient and tonic activity changes, including delay cell activity, were observed as in other behavioral tasks. When exposed to the context without CS delivery, most units changed their activities as well. These results show that both tone and contextual information are processed in the rat mPFC in expectation of the delivery of an aversive stimulus (electric foot shock). Interestingly, fast spiking cells (putative inhibitory interneurons) and regular spiking cells (putative projection neurons) showed different patterns of responses. Fast spiking cells tended to show transient responses and increased their firing rates following CS presentation, whereas a complementary pattern was observed in the regular spiking cells. Our results enhance our understanding of the neural mechanisms underlying prediction of an aversive stimulus in the mPFC.

Acoustic Stimulation↗
PubMed2004

Pathologic fear conditioning and anorexia nervosa: on the search for novel paradigms.

Although eating disorders have been the focus of an unprecedented explosion of clinical interest in recent years, the etiology of anorexia nervosa remains elusive. It is hypothesized that an underlying causative mechanism involves a propensity to extreme fear conditioning and greater than normal resistance to its extinction. Knowledge accrued from recent behavioral, genetic, and neuroanatomic research on anxiety may yield further insight into the pathogenesis of anorexia nervosa, which can be subjected to experimental validation using objective measures of classical fear conditioning and functional neuroimaging of brain structures mediating fear behavior.

Adolescent↗
PubMed2002

Blockade of alpha1 adrenoreceptors in the dorsal raphe nucleus prevents enhanced conditioned fear and impaired escape performance following uncontrollable stressor exposure in rats.

Previous research has shown that the effect of exposure to uncontrollable stressors on conditioned fear responding and escape behavior in rats is dependent on serotonergic neural activity in the dorsal raphe nucleus (DRN). The role that norepinephrine released in the DRN plays in producing the behavioral consequences of exposure to inescapable tail shock in rats was investigated in the present study. The selective alpha1 adrenoreceptor antagonist benoxathian was injected into the DRN before exposure to inescapable tail shock or before behavioral testing conducted 24 h later. Benoxathian prevented the impairment of escape responding produced by inescapable shock, but did not reverse this effect when given before testing. The enhancement of conditioned fear produced by prior inescapable shock was attenuated by benoxathian administered before inescapable shock or before behavioral testing. These results support the view that noradrenergic input to the DRN is necessary to produce the behavioral effects of inescapable tail shock.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1996

Serotonin reuptake inhibitors reduce conditioned fear stress-induced freezing behavior in rats.

Conditioned fear stress (CFS)-induced freezing behavior has been proposed as an animal model of anxiety. In the present study, freezing was used to determine the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs), which are reported to be clinically effective in anxiety disorders. The duration of freezing behavior was reduced by acute treatment with the SSRIs citalopram (1-10 mg/kg) and fluvoxamine (3-30 mg/kg). Acute treatment with the serotonin (5-HT)/noradrenaline (NA) mixed reuptake inhibitor milnacipran (3-30 mg/kg) also attenuated CFS-induced freezing, while acute treatment with the NA reuptake inhibitors maprotiline and ORG4428, and the dopamine (DA) reuptake inhibitor GBR12909 failed to alter CFS-induced freezing. These results indicate that facilitation of 5-HT availability in the brain produced by 5-HT reuptake inhibition reduces CFS-induced freezing behavior. CFS may be a useful model for detecting the anxiolytic potential of 5-HT reuptake inhibitors.

Animals↗
PubMed2004

Perirhinal cortex supports delay fear conditioning to rat ultrasonic social signals.

Auditory information can reach the lateral nucleus of the amygdala (LA) through a monosynaptic thalamic projection or a polysynaptic cortical route. The polymodal input from the perirhinal cortex (PR) is a major informational gateway to the LA and nearby structures. Pretraining PR lesions impair fear conditioning to a context, but there have been no reports that they cause deficits in delay conditioning to an auditory cue. The direct subcortical projection to the LA seems sufficient to support delay conditioning to a tone conditional stimulus (CS). We examined the effect of PR lesions on delay conditioning to two different tone conditional stimuli (4 and 22 kHz tones; both 10 sec duration) and two different rat ultrasonic vocalization (USV) conditional stimuli (10 sec of "22 kHz USVs"). The two USV conditional stimuli were multi-call segments that were recorded (digitized at 100 kHz) from two different rats. One USV CS was a continuous sequence of eight calls, and the other was a portion of a continuous sequence of six calls. PR lesions significantly impaired conditioning to both USV conditional stimuli and to the training context but had no significant effect on conditioning to either tone CS. The role of PR in fear conditioning appears not to be determined by whether the conditional stimuli serve as contexts or cues, but instead by the nature or complexity of the stimuli or stimulus configurations. These cue-specific effects of PR lesions are suggested to reflect differences in the stimulus features that are encoded in the two CS pathways to the LA.

Acoustic Stimulation↗
PubMed2005

The ventral hippocampus supports a memory representation of context and contextual fear conditioning: implications for a unitary function of the hippocampus.

The authors report that either inactivating the ventral hippocampus (VH) with muscimol prior to context preexposure or injecting anisomycin into the VH after preexposure significantly impaired rats' memory for context. Injecting anisomycin into the VH prior to contextual fear conditioning also greatly reduced long-term memory (48-hr retention test) but had no effect on short-term memory (1-hr retention test) for contextual fear. Together with other results, these data suggest that the memory for a novel context is distributed throughout the longitudinal extent of the hippocampus and that this representation helps to support contextual fear conditioning.

Animals↗