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At least 973 records · Page 54Linked to original sources
PubMed2001

Fear conditioning-induced alterations of phospholipase C-beta1a protein level and enzyme activity in rat hippocampal formation and medial frontal cortex.

We investigated the effects of one-trial fear conditioning on phospholipase C-beta1a catalytic activity and protein level in hippocampal formation and medial frontal cortex of untreated control rats and rats prenatally exposed to ethanol. One hour following fear conditioning of untreated control rats, phospholipase C-beta1a protein level was increased in the hippocampal cytosolic fraction and decreased in the hippocampal membrane and cortical cytosolic and cortical membrane fractions. Twenty-four hours after fear conditioning, phospholipase C-beta1a protein level was reduced in the hippocampal cytosolic fraction and elevated in the cortical nuclear fraction; in addition, 24 h after conditioning, phospholipase C-beta1a activity in the cortical cytosolic fraction was increased. Rats that were exposed prenatally to ethanol displayed attenuated contextual fear conditioning, whereas conditioning to the acoustic-conditioned stimulus was not different from controls. In behavioral control (unconditioned) rats, fetal ethanol exposure was associated with reduced phospholipase C-beta1a enzyme activity in the hippocampal nuclear, cortical cytosolic, and cortical membrane fractions and increased phospholipase C-beta1a protein level in the hippocampal membrane and cortical cytosolic fractions. In certain cases, prenatal ethanol exposure modified the relationship between fear conditioning and changes in phospholipase C-beta1a protein level and/or activity. The majority of these effects occurred 1 h, rather than 24 h, after fear conditioning. Multivariate analysis of variance revealed interactions between fear conditioning, subcellular fraction, and prenatal ethanol exposure for measures of phospholipase C-beta1a protein level in hippocampal formation and phospholipase C-beta1a enzyme activity in medial frontal cortex. In the majority of cases, fear conditioning-induced changes in hippocampal phospholipase C-beta1a protein level were augmented in rats prenatally exposed to ethanol. In contrast, fear conditioning-induced changes in cortical phospholipase C-beta1a activity were, often, in opposite directions in prenatal ethanol-exposed compared to diet control rats. We speculate that alterations in subcellular phospholipase C-beta1a catalytic activity and protein level contribute to contextual fear conditioning and that learning deficits observed in rats exposed prenatally to ethanol result, in part, from dysfunctions in phospholipase C-beta1a signal transduction.

Acoustic Stimulation↗
PubMed2004

Role of amygdala in conditioned and unconditioned fear generated in the periaqueductal gray.

The amygdala and ventral portion of the periaqueductal gray (vPAG) are crucial for the expression of the contextual freezing behavior. However, it is still unclear whether the amygdala also plays a role in defensive behaviors induced by electrical stimulation of the dorsal periaqueductal gray (dPAG). In the present study, rats were implanted with electrodes into dPAG for determination of the thresholds for freezing and escape responses before and after sham or electrolytic lesions in the amygdala. Animals were then submitted to a context fear conditioning procedure. Amygdala lesions disrupted contextual freezing but did not affect defensive behaviors induced by dPAG electrical stimulation. These results indicate that contextual and unconditioned freezing behaviors are mediated by independent neural circuits.

Amygdala↗
PubMed2002

Neurons in medial prefrontal cortex signal memory for fear extinction.

Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.

Acoustic Stimulation↗
PubMed1994

NMDA receptor antagonist MK-801 blocks learning of conditioned stimulus-unconditioned stimulus contiguity but not fear of conditioned stimulus in goldfish (Carassius auratus L.).

The blockade of learning of Pavlovian fear conditioning by the N-methyl-D-aspartic acid (NMDA)-receptor antagonist MK-801 was examined in 166 goldfish. In previously untrained fish, MK-801 blocked learning of a light-off or a tone conditioned stimulus (CS) paired with an electrical shock unconditioned stimulus (US). Pretraining on the light-off CS did not affect the rate of learning of the tone CS but protected the tone learning from disruption by MK-801. Switching from the light-off to the tone CS changed the identity of the CS but not its temporal contiguity with the US. Pretraining consisting of pseudoconditioning of the light-off CS did not protect subsequent tone learning from blockade by MK-801. Thus, the NMDA receptor functions are necessary for learning related to the temporal contiguity of the CS and US but not to the identity of the CS as a cue to the occurrence of the fearful effects of the US.

Acoustic Stimulation↗
PubMed2007

5-HT2 receptor mechanisms of the dorsal periaqueductal gray in the conditioned and unconditioned fear in rats.

RATIONALE: It is well known that 5-HT(2) mechanisms modulate the defensive behavior produced by the stimulation of the dorsal periaqueductal gray (dPAG). However, in spite of the notion that past stressful experiences play a role in certain types of anxiety, only studies with the stimulation of the dPAG of rats without previous aversive experience have been conducted so far. OBJECTIVES: We investigated the mediation of 5-HT(2) receptors of the dPAG in rats previously submitted to contextual fear conditioning (CFC). Defensive behaviors induced by the activation of the dPAG were assessed by measuring the lowest intensity of electric current applied to this structure (threshold) able to produce freezing and escape responses during the testing sessions of CFC in which animals were placed in a context previously paired to footshocks. The 5-HT(2) function of the dPAG in this condition was evaluated by local injections of alpha-methyl-5-HT (20 nmol/0.2 mul) and ketanserin (5 and 10 nmol/0.2 mul), selective agonist and antagonist of 5-HT(2) receptors, respectively. RESULTS: In accordance with previous studies, alpha-methyl-5-HT increased the aversive thresholds (antiaversive effects) in naive rats, and injection of ketanserin into the dPAG did not produce significant effects. On the other hand, ketanserin decreased in a dose-dependent manner the freezing threshold (proaversive effect) determined by the dPAG electrical stimulation, whereas alpha-methyl-5-HT continued to show antiaversive effects in animals under CFC. CONCLUSIONS: The present results suggest that past stressful experience can produce changes in the synaptic function of 5-HT(2) receptors within the dPAG with important impact on the expression of defensive behaviors.

Animals↗
PubMed2005

Heart rate dynamics and behavioral responses during acute emotional challenge in corticotropin-releasing factor receptor 1-deficient and corticotropin-releasing factor-overexpressing mice.

The role of corticotropin-releasing factor in autonomic regulation of heart rate, heart rate variability and behavior responses was investigated in two genetic mouse models: corticotropin-releasing factor receptor 1-deficient mice, and corticotropin-releasing factor-transgenic mice overexpressing corticotropin-releasing factor. Heart rate was recorded by radio-telemetry during novelty exposure and auditory fear conditioning. Locomotor activity and freezing served as behavioral indices. Locomotor activity and heart rate were invariably increased in response to novelty exposure in both corticotropin-releasing factor receptor 1-deficient mice and littermate wild-type controls. The heart rate responses during retention of conditioned auditory fear and the exponential relationship between heart rate and heart rate variability were unaffected by genotype. Moreover, conditioned fear responses inferred from multiple behavioral measures including freezing did not differ between corticotropin-releasing factor receptor 1-deficient and corticotropin-releasing factor receptor 1 wild-type control mice. Corticotropin-releasing factor-transgenic mice exhibited markedly reduced locomotor activity during novelty exposure when compared with littermate wild-type controls. Baseline and novelty-driven heart rate was slightly elevated in corticotropin-releasing factor-transgenic mice, whereas the novelty-induced increase of heart rate was not different between genotypes. In contrast, corticotropin-releasing factor-transgenic mice did not display a heart rate response indicative of conditioned auditory fear. It is concluded that corticotropin-releasing factor receptor 1-deficiency does not affect heart rate adjustment and behavioral responses to acute fearful stimuli. The resiliency of behavioral and cardiovascular patterns elevation argues against the involvement of corticotropin-releasing factor receptor 1 in acute emotional regulation on these two functional levels despite an absent corticosterone elevation in corticotropin-releasing factor receptor 1-deficient mice. It is hypothesized that the lack of a conditioned heart rate response in corticotropin-releasing factor-transgenic mice is attributable to an impairment of cognitive function. The results are compared with those of corticotropin-releasing factor receptor 2-deficient mice, and the role of the corticotropin-releasing factor system in cardiovascular regulation is discussed.

Animals↗
PubMed2000

Selective corticotropin-releasing factor type 1 receptor antagonist blocks conditioned fear-induced release of noradrenaline in the hypothalamic paraventricular nucleus of rats.

The effects of conditioned fear on the release of noradrenaline in the hypothalamic paraventricular nucleus (PVN) and the involvement of corticotropin-releasing factor (CRF) receptor type 1 (CRFR1) in conditioned fear-induced changes in noradrenaline release were examined by intracerebral microdialysis in rats. Conditioned fear was produced by placing animals into a box where they had previously been exposed to a 5-min period of electric footshock, 135 min prior to the start of experiment. Conditioned fear for 20 min produced a significant increase in the release of noradrenaline in the PVN. Intraperitoneal preadministration of a selective nonpeptidic CRFR1 antagonist, CRA1000, completely blocked the conditioned fear-induced release of noradrenaline. These results suggest that CRFR1 is involved in the release of noradrenaline in the hypothalamic PVN induced by conditioned fear.

Animals↗
PubMedDate not supplied

Effects of the selective M1 muscarinic receptor antagonist dicyclomine on emotional memory.

The nonselective muscarinic antagonist scopolamine is known to impair the acquisition of some learning tasks such as inhibitory avoidance. There has been recent research into the effects of this drug in contextual fear conditioning and tone fear conditioning paradigms. The purpose of the present study was to assess the role of the selective M1 muscarinic antagonist dicyclomine in these paradigms and in the inhibitory avoidance test. Rats were administered different doses of dicyclomine or saline 30 min before acquisition training. The animals were tested 24 hr later, and it was observed that 16 mg/kg of dicyclomine impaired both contextual fear conditioning and inhibitory avoidance. However, dicyclomine (up to 64 mg/kg) did not affect tone fear conditioning. These results suggest that the selective M1 muscarinic antagonist dicyclomine differentially affects aversively motivated tasks known to be dependent on hippocampal integrity (such as contextual fear conditioning and inhibitory avoidance) but does not affect similar hippocampus-independent tasks.

Acoustic Stimulation↗
PubMed2001

NMDA-mediated social learning of fear-induced conditioned analgesia to biting flies.

Although fear conditioning has received extensive neurobiological attention little is known about social learning whereby one individual may learn and acquire the fear responses of another. A 30 min exposure to intact biting flies (stable fly, Stomoxys colcitrans L.) elicits in individual fly-naive mice analgesia and active self burying responses to avoid the flies. Fly-naive observer mice that witnessed other demonstrator mice being attacked by biting flies exhibited analgesia and self-burying to avoid flies when exposed 24 h later to altered flies whose biting mouth parts were removed. The opiate antagonist naloxone, while reducing the analgesic responses elicited by exposure to a fly-stressed demonstrator, did not affect either the subsequent conditioned analgesia or self-burying. However, the specific NMDA receptor antagonist NPC 12626, given to observers prior to, but not after, presentation of fly attacked demonstrators blocked the socially determined conditioned analgesia and self burying avoidance. This supports NMDA involvement in the mediation of the social transmission and long-term (24h) retention of conditioned analgesia and fear.

Amino Acids↗
PubMed2006

Hyperarousal does not depend on trauma-related contextual memory in an animal model of Posttraumatic Stress Disorder.

Both classical fear conditioning and fear sensitization have been implicated in the development of Posttraumatic Stress Disorder (PTSD), but little is known about their interaction or interdependency. Therefore, we administered the NMDA receptor antagonist AP5 or vehicle bilaterally into the dorsal hippocampus of C57BL/6N mice 15 min before administration of an electric footshock. One month later mice were tested for their conditioned fear reaction to the shock context (associative fear memory) and for their sensitized fear response to a neutral tone in a new context (hyperarousal). AP5-treated animals exhibited only half as much conditioned, but equal amounts of sensitized fear, compared to vehicle-treated mice, demonstrating that hyperarousal does not depend on associative fear memory about the aversive encounter, but solely on sensitization induced by the inescapable footshock. This result points to the need for a 'desensitization' approach in PTSD therapy, as sensitization and classical conditioning seem to be independent processes in this psychiatric disorder.

2-Amino-5-phosphonovalerate↗
PubMed2005

Deletion of the mu opioid receptor results in impaired acquisition of Pavlovian context fear.

The mu opioid receptor may constitute a critical component of a negative feedback system that regulates Pavlovian fear conditioning. We investigated context fear conditioning acquisition and expression in mu opioid receptor knockout mice (on an inbred, C57 genetic background). We discovered that the mu receptor knockout results in an unexpected and significant deficit in context fear acquisition. Mice lacking the mu receptor showed normal fear acquisition when subjected to a 1-day fear conditioning protocol but evinced deficient fear learning when acquisition was conducted across 5 days. The knockout mice showed normal reactivity to footshock in both fear conditioning protocols. Finally, we confirmed the effectiveness of the receptor deletion in the C57 strain by subjecting the mice to a test of morphine analgesia in the hot-plate assay. As has been seen with mixed genetic background, the receptor deletion resulted in a complete lack of analgesic response to 10 mg/kg morphine. Surprisingly, mice with a single copy of the mu receptor gene (heterozygous knockouts) showed intact sensitivity to morphine but a significant deficit in Pavlovian fear conditioning. The results indicate that deletion of the mu receptor gene impairs fear conditioning and that the conditioning and analgesia effects of heterozygous deletion are dissociable. The conditioning deficit seen in this line of mice may be related to impairment in hippocampus function.

Analgesics, Opioid↗
PubMed1993

Visual cortex ablations do not prevent extinction of fear-potentiated startle using a visual conditioned stimulus.

Following observations in the literature that sensory cortex ablations prevent extinction of conditioned fear, the present experiments tested the generality of this finding by examining whether visual cortex ablations would prevent extinction of conditioned fear as assessed by fear-potentiated startle using a visual conditioned stimulus. Consistent with previous reports, visual cortex ablations did not prevent the acquisition or expression of fear-potentiated startle to a visual conditioned stimulus. More importantly, visual cortex ablations did not prevent extinction of fear-potentiated startle to a visual conditioned stimulus, nor did they reverse preoperatively established extinction, indicating that sensory cortex is not required for extinction of conditioned fear in all situations.

Animals↗
PubMed2001

Learning from others to cope with biting flies: social learning of fear-induced conditioned analgesia and active avoidance.

Although fear conditioning has received extensive attention, little is known about the roles of social learning whereby an individual may learn and acquire the fear responses of another. The authors examined individually and socially mediated acquisition of fear and analgesia to the natural aversive stimulus of biting flies. Exposure to biting flies elicited in individual naive mice analgesia and active self-burying to avoid the flies. When exposed 24 hr later to flies whose biting parts were removed, but not to nonbiting house flies, these mice displayed conditioned analgesia and self-burying. This "one-trial" conditioned analgesia and avoidance was also acquired through social learning without direct individual experience with biting flies. Naive "observer" mice that witnessed other "demonstrator" mice being attacked by biting flies exhibited analgesia and self-burying 24 hr later to altered flies.

Adaptation, Psychological↗
PubMed2007

Persistent disruption of a traumatic memory by postretrieval inactivation of glucocorticoid receptors in the amygdala.

BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, which include alterations in glucocorticoid secretion and critically involve the limbic system, in particular the amygdala. Important symptoms of PTSD manifest as a classical conditioning to fear, which recurs each time trauma-related cues remind the subject of the original insult. Traumatic memories based on fear conditioning can be disrupted if interfering events or pharmacological interventions are applied following their retrieval. METHODS AND RESULTS: Using an animal model, here we show that a traumatic memory is persistently disrupted if immediately after its retrieval glucocorticoid receptors are inactivated in the amygdala. The disruption of the memory is long lasting and memory retention does not re-emerge following strong reminders of the conditioned fear. CONCLUSIONS: We propose that a combinatorial approach of psychological and pharmacological intervention targeting the glucocorticoid system following memory retrieval may represent a novel direction for the treatment of PTSD.

Amygdala↗
PubMed1999

The impact of the nonpeptide corticotropin-releasing hormone antagonist antalarmin on behavioral and endocrine responses to stress.

The nonpeptide CRH antagonist antalarmin has been shown to block both behavioral and endocrine responses to CRH. However, it's potential activity in blunting behavioral and endocrine sequelae of stressor exposure has not been assessed. Because antagonism of central CRH by alpha-helical CRH attenuates conditioned fear responses, we sought to test antalarmin in this regard. In addition, it remains unclear as to whether this is a result of receptor blockade during conditioning or during testing. Thus, we explored whether CRH mediates the induction or expression of conditioned fear (freezing in a context previously associated with 2 footshocks; 1.0 mA, 5 sec each). Furthermore, because rats previously exposed to inescapable shock (IS; 100 shocks, 1.6 mA, 5 sec each), demonstrate enhanced fear conditioning, we investigated whether this effect would be blocked by antalarmin. Antalarmin (20 mg/kg x 2 ml i.p.) impaired both the induction and expression of conditioned fear. In addition, antalarmin blocked the enhancement of fear conditioning produced by prior exposure to IS. Despite the marked behavioral effects observed in antalarmin-treated rats, antalarmin had no effect on IS-induced rises in ACTH or corticosterone. However, antalarmin did block the ACTH response produced by exposure to 2 footshocks.

Adrenal Cortex Hormones↗
PubMed1997

Hippocampal lesions alter conditioning to conditional and contextual stimuli.

The control of conditioned fear behaviour by a conditional stimulus (CS) and contextual stimuli (CXT) was compared in rats with lesions to the hippocampus (HPC) or neocortex (CO), and operated controls (OC). After classical fear conditioning in a distinctive context, rats were subsequently tested in the presence of the CS and CXT (CS + CXT), the CS alone (CS-only), or context alone (CXT-only). Two experiments were conducted in which conditioned fear was measured by an active avoidance response (experiment 1) or by response suppression (experiment 2). Groups did not differ in acquiring the conditioned fear response, as measured in the CS + CON test but, in both experiments, hippocampal (HPC) groups exhibited more conditioned fear behaviour than controls in the CXT-Only and CS-Only conditions. It was suggested that control rats conditioned the fear response to a stimulus complex that incorporated the CS and CTX. Rats with HPC lesions did not form this association between the stimulus elements; instead they segregated the CS and CXT and formed independent associations between the conditioned response (CR) and each component. In showing that HPC damage disrupts the process of forming associations between environmental stimuli and that the effect is not restricted to contextual cues, the results help to resolve apparently contradictory findings regarding the role of HPC in contextual information processing.

Animals↗
PubMed1999

Long-term potentiation in the amygdala: a mechanism for emotional learning and memory.

In the mammalian brain, LTP is an enduring form of synaptic plasticity that is posited to have a role in learning and memory. Compelling new evidence for this view derives from studies of LTP in the amygdala, a brain structure that is essential for simple forms of emotional learning and memory, such as Pavlovian fear conditioning in rats. More specifically, antagonists of the NMDA receptor block both amygdaloid LTP induction and fear conditioning, fear conditioning induces increases in amygdaloid synaptic transmission that resemble LTP, and genetic modifications that disrupt amygdaloid LTP eliminate fear conditioning. Collectively, these results provide the most-convincing evidence to date that LTP mediates learning and memory in mammals.

Amygdala↗
PubMed2004

Performance in long-term memory tasks is augmented by a phosphorylated growth factor receptor fragment.

To elucidate the role of enhanced phosphoinositide-3-kinase (PI3-kinase) activity in memory, a synthetic phosphopeptide (TAT-YPMDM) containing the p85 regulatory subunit receptor-binding motif (YXXM) coupled to the cell transduction domain of HIV-TAT protein was employed. This phosphopeptide bound the p85 subunit of PI3-kinase, and was internalized by both granule and pyramidal neurons when injected into the hippocampus. Increased lipid kinase activity and enhanced phosphorylation of the PI3-kinase substrates Akt (protein kinase B) and ribosomal S6 kinase were associated with TAT-YPMDM administration. Bilateral infusion of the phosphopeptide into the dorsal hippocampus after training improved performance in three hippocampus-dependent memory tasks: contextual fear conditioning, trace fear conditioning, and the Morris water maze. Both the biochemical and behavioral effects of the TAT-YPMDM phosphopeptide could be blocked by wortmannin. No effect was observed when a nonphosphorylated peptide (TAT-YMDM), or a second, unrelated phosphopeptide (TAT-YPLDL) was utilized. In addition, infusion of the TAT-YPMDM phosphopeptide did not interfere with memory acquisition or 4 hr memory. In addition, pretesting administration did not affect the ability to recall a previously established long-term memory. These findings suggest that stimulation of PI3-kinase activity by phosphorylated receptor fragments containing the YMDM motif augments long-term memory.

Amino Acid Motifs↗