Neuroendocrine and behavioral responses during conditioned active and passive behavior in the defensive burying/probe avoidance paradigm: Effects of ipsapirone

Korte, S. Mechiel; Bouws, G.A.H.; Koolhaas, Jaap M.; Bohus, B.

doi:10.1016/0031-9384(92)90284-9

Cited by 62 publications

(23 citation statements)

References 54 publications

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“…Thus, it is not likely that the molecular mechanisms underlying extinction are similar to those for acquisition of contextual freezing, as it has been previously suggested for inhibitory avoidance (Szapiro et al, 2003). Because both behaviors similarly depend on contextual memory retrieval, some of the observed discrepancies may be attributable to differences in the intensity of contextual fear (Rachman & Hodgson, 1974) and stress hormone levels (Korte et al, 1992) accompanying avoidance versus immobility.…”

Section: Discussionmentioning

confidence: 91%

Hippocampal Mek/Erk signaling mediates extinction of contextual freezing behavior

Fischer

Radulović

Schrick

et al. 2007

Neurobiology of Learning and Memory

100

103

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Fear memories elicit multiple behavioral responses, encompassing avoidance or behavioral inhibition in response to threatening contexts. Context-specific freezing, reflecting fear-induced behavioral inhibition, has been proposed as one of the main risks factors for the development of anxiety disorders. We attempted to define the key hippocampal mediators of extinction in a mouse model of context-dependent freezing. Nine-week-old male C57BL/6J mice were trained and tested for contextual fear conditioning and extinction. Freezing behavior scored by unbiased sampling, was used as an index of fear. Proteomic, immunoblot and immunohistochemical approaches were employed to identify, verify and analyze the alterations of the hippocampal extracellular signalregulated kinases 1 and 2 (Erk-1/2). Targeted pharmacological inhibition of the Erk-1/2 activating kinase, the mitogen activated and extracellular signal-regulated kinase (Mek), served to establish the role of Mek/Erk signaling in extinction. When compared to acquisition, extinction of contextual freezing triggered a rapid activation of Erk-1/2 showing a distinctive time-course, nuclear localization and subcellular isoform distribution. These differences suggested that the upstream regulation and downstream effects of this pathway might be specific for each process. Dorsohippocampal injections of the Mek inhibitors U0126 (0.5 μg/site) and PD98059 (1.5 μg/site) immediately after the nonreinforced trials prevented Erk-1/2 activation and significantly impaired extinction. This effect was dissociable from potential actions on memory retrieval or reconsolidation. On the basis of these findings, we propose that hippocampal Mek/Erk signaling might serve as one of the key mediators of contextual fear extinction.

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Section: Discussionmentioning

confidence: 91%

Hippocampal Mek/Erk signaling mediates extinction of contextual freezing behavior

Fischer

Radulović

Schrick

et al. 2007

Neurobiology of Learning and Memory

100

103

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“…CRF administration has been shown to increase probe burying, while this behavior was blocked by CRF antagonists (Basso et al 1999;Diamant et al 1992;Korte et al 1994). Furthermore, shock-probe burying is accompanied by increases in NE transmission (Bondi et al 2007;Korte et al 1992) and attenuated by pretreatment with noradrenergic antagonists (Morilak et al 2005). Taken together, these data suggest that burying by rodents may be a model response for stress associated with the activation of NE pathways from the LC.…”

Section: Burying Behavior Is Mediated By Forebrain Nementioning

confidence: 86%

“…Rodent burying behavior has long been described as a defensive coping strategy in natural habitats (Calhoun 1962;MacClintock 1970;Owings and Coss 1977). Furthermore, in the context of defensive avoidance, this proactive form of stress management provides an index of anxiety when directed at an electrified probe (Bondi et al 2007;De Boer et al 1990;Korte et al 1992;Treit et al 1981), and is enhanced and attenuated by anxiogenic and anxiolytic drugs, respectively (De Boer and Koolhaas 2003;Diamant et al 1992). To the best of our knowledge, the present studies are the first to specifically characterize and quantify the burying response to i.c.v.…”

Section: Characterization Of Crf-evoked Behaviorsmentioning

confidence: 99%

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

et al. 2008

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Rationale-Central administration of corticotropin-releasing factor (CRF) elicits a specific pattern of behavioral responses resembling a stress-like state, and is anxiogenic in rodent models of anxiety.Objectives-Specific behaviors evoked by the administration of CRF were measured. The roles of CRF receptor subtypes and that of serotonergic and noradrenergic systems in mediating these responses were studied.Methods-Burying, grooming and head shakes were quantified in rats following intracerebroventricular administration of CRF and urocortin II and after pretreatment with antagonists. The role of forebrain norepinephrine in the behavioral responses to CRF (0.3 μg) was examined following pretreatment with the neurotoxin DSP-4 and that of serotonin after depletion using systemic administration of para-chlorophenylalanine (p-CPA).Results-CRF at 0.3 and 3.0 μg caused robust increases in burying, grooming and head shakes, but urocortin II was ineffective. Pretreatment with either antalarmin or propranolol significantly attenuated the CRF-evoked behaviors. Destruction of forebrain NE pathways blocked spontaneous burying behavior elicited by CRF and conditioned burying directed towards an electrified shock probe. In contrast, depletion of 5-HT selectively attenuated CRF-evoked grooming.Conclusions-Overt behavioral responses produced by CRF, burying, grooming, and head shakes, appeared to be mediated through the CRF 1 receptor. Spontaneous burying behavior evoked by CRF or conditioned burying directed towards a shock probe were disrupted by lesion of the dorsal noradrenergic bundle and may represent anxiety-like behavior caused by CRF activation of the LC. In contrast, CRF-evoked increases in grooming were dependent on serotonin.

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“…Based on naturalistic observations of rodents' behaviors in response to predators in the wild, the DB test measures differences in coping strategies (Koolhaas et al, 1999;Korte et al, 1992;Pare, 1994;Sluyter et al, 1996;Treit, 1985;Treit et al, 1981) by assaying an animal's behavioral response to an immediate threat with ethological validity (Treit, 1991). In the DB test, the animal unexpectedly receives a mild electric shock, which represents the immediate danger.…”

Section: Introductionmentioning

confidence: 99%

Lineage is an Epigenetic Modifier of QTL Influencing Behavioral Coping with Stress

et al. 2005

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A genome-wide scan was carried out on a segregating F2 population of rats derived from reciprocal intercrosses between two inbred strains of rats, Fisher 344 (F344) and Wistar Kyoto (WKY) that differ significantly in their behavioral coping responses to stress measured by the defensive burying (DB) test. The DB test measures differences in coping strategies by assaying an animal's behavioral response to an immediate threat. We have previously identified three X-linked loci contributing to the phenotypic variance in behavioral coping. Here we report on six significant autosomal quantitative trait loci (QTL) related to different behaviors in the DB test:one for the number of shocks received, three for number of prod approaches, one for latency to bury, and one pleiotropic locus affecting both approach and latency. These QTL contributing to different aspects of coping behaviors show that the effect of genotype on phenotype is highly dependent on lineage. The WKY lineage was particularly influential, with five out of the six QTL affecting coping behavior only in rats of the WKY lineage, and one locus affecting only those in the F344 lineage. Thus, epigenetic factors, primarily of WKY origin, may significantly modulate the genetic contribution to variance in behavioral responses to stress in the DB test.

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Neuroendocrine and behavioral responses during conditioned active and passive behavior in the defensive burying/probe avoidance paradigm: Effects of ipsapirone

Cited by 62 publications

References 54 publications

Hippocampal Mek/Erk signaling mediates extinction of contextual freezing behavior

Hippocampal Mek/Erk signaling mediates extinction of contextual freezing behavior

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

Lineage is an Epigenetic Modifier of QTL Influencing Behavioral Coping with Stress

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