Stress and central Urocortin increase anxiety-like behavior in the social interaction test via the CRF1 receptor

Gehlert, Donald R.; Shekhar, Anantha; Morin, Stéphanie; Hipskind, P; Zink, Charity; Gackenheimer, Susan L.; Shaw, Janice; Fitz, Stephanie D.; Sajdyk, Tammy J.

doi:10.1016/j.ejphar.2004.12.030

Cited by 92 publications

(74 citation statements)

References 53 publications

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“…The role of CRF 1 receptors in grooming is supported by evidence from previous investigations (Bressers et al 1995;de Groote et al 2005;Drago et al 1999;Lumley et al 2001;Ohata and Shibasaki 2004). Taken together, these findings are consistent with the proposed role of CRF 1 receptors in mediating stress-like behavioral responses and anxiogenic effects of CRF (Arborelius et al 2000;Gehlert et al 2005;Griebel et al 2002;Zorrilla et al 2002). The attenuation of behaviors following antalarmin pretreatment was only observed in CRF-infused animals and not in aCSF-infused controls indicating that they are likely not due to non-specific effects on locomotion or exploratory behavior.…”

Section: Characterization Of Crf-evoked Behaviorssupporting

confidence: 84%

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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Section: Characterization Of Crf-evoked Behaviorssupporting

confidence: 84%

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

et al. 2008

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“…For example, pharmacological activation of CRHR1 centrally was found to decrease social exploration in rats (Dunn and File, 1987;Campbell et al, 2004;Gehlert et al, 2005), an effect that was also observed when the amygdala was directly targeted (Sajdyk et al, 1999;Gehlert et al, 2005;Spiga et al, 2006). In agreement with our pharmacological data, prior evidence has also shown that antagonizing CRHR1 has no effect on social behaviors (in our study, the antagonist led to a non-significant reduction in social interaction) but is effective in abolishing the deficits induced by enhanced CRH function on sociability (Sajdyk and Gehlert, 2000;Gehlert et al, 2005). In this context, it should be noted that CRH antagonists have been considered promising candidates for the treatment of social phobia in humans (van Ameringen et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors

Veenit

Riccio

Sandi

2014

Journal of Psychiatric Research

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a b s t r a c tStressful life events during childhood and adolescence are important risk factors for the development of psychopathologies later in life. The corticotropin releasing hormone (CRH) and the CRH receptor 1 (CRHR1) have been implicated in the link between early life adversity and adult anxiety and depression, with rodent studies identifying the very early postnatal period as highly susceptible to this programming. Here, we investigated whether stress exposure during the peripubertal period e comprising juvenility and puberty e is effective in inducing long-lasting changes in the expression of CRHR1 and CRHR2 in the hippocampus and amygdala, and whether treating animals with a CRHR1 antagonist following stress exposure could reverse behavioral alterations induced by peripuberty stress. We show that peripuberty stress leads to enhanced expression of the Crhr1, but not Crhr2, gene in the hippocampal CA1 and the central nucleus of the amygdala, in association with social deficits in the social exploration test and increased stress-coping behaviors in the forced swim test. Treatment with the CRHR1 antagonist NBI30775 (10 mg/kg) daily for 1 week (from P43 to P49), immediately following peripuberty stress exposure, prevented the occurrence of those psychopathological behaviors at adulthood. These findings highlight peripuberty as a period of plasticity for the enduring modulation of the CRHR1 system and support a growing body of data implicating the CRHR1 system in the programming effects of early life stress on eventual psychopathology. They also support recent evidence indicating that temporarily tackling CRHR1 during development might represent a therapeutic opportunity to correct behavioral trajectories linking early stress to adult psychopathology.

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“…The social-interaction test is sensitive to the anxiogenic and anxiolytic effects of drugs (File and Seth, 2003). Exposure to stressors decreases social interaction in rats (Morilak et al, 2003), and this effect is reversed by CRF 1 receptor antagonists (Gehlert et al, 2005). We used the social-interaction test to independently verify that under our experimental conditions, yohimbine induces stress-and anxiety-like responses that are reversed by antalarmin.…”

Section: Methodsmentioning

confidence: 99%

The Anxiogenic Drug Yohimbine Reinstates Palatable Food Seeking in a Rat Relapse Model: a Role of CRF1 Receptors

Ghitza

Gray

Epstein

et al. 2005

Neuropsychopharmacol

142

156

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The major problem in treating excessive eating is high rates of relapse to maladaptive eating habits during diet treatments; this relapse is often induced by stress or anxiety states. Preclinical studies have not explored this clinical problem. Here, we adapted a reinstatement model (commonly used to study relapse to abused drugs) to examine the role of stress and anxiety in relapse to palatable food seeking during dieting. Rats were placed on restricted diet (75-80% of daily standard food) and for 12 intermittent training days (9 h/day, every other day) lever-pressed for palatable food pellets (25% fat, 48% carbohydrate) under a fixed ratio 1 (20-s timeout) reinforcement schedule. Subsequently, the rats were given 10 daily extinction sessions during which lever presses were not reinforced, and were then injected with yohimbine (an a-2 adrenoceptor antagonist that induces stress and anxiety in humans and non-humans) or given a single food pellet to assess reinstatement of food seeking. The rats rapidly learned to lever press for the palatable pellets and across the training days the ratio of timeout nonreinforced lever presses to reinforced lever presses progressively increased more than three-fold, suggesting the development of compulsive eating behavior. After extinction, yohimbine injections and pellet priming reliably reinstated food seeking. The corticotropin-releasing factor 1 (CRF 1 ) receptor antagonist antalarmin attenuated the reinstatement induced by yohimbine, but not pellet priming. Antalarmin also reversed yohimbine's anxiogenic effects in the social interaction test. These data suggest that CRF is involved in stress-induced relapse to palatable food seeking, and that CRF 1 antagonists should be considered for the treatment of maladaptive eating habits.

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Stress and central Urocortin increase anxiety-like behavior in the social interaction test via the CRF1 receptor

Cited by 92 publications

References 53 publications

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

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

CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors

The Anxiogenic Drug Yohimbine Reinstates Palatable Food Seeking in a Rat Relapse Model: a Role of CRF1 Receptors

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