Role of corticotropin-releasing factor and urocortin within the basolateral amygdala of rats in anxiety and panic responses

Sajdyk, Tammy J.; Schober, Douglas A.; Gehlert, Donald R.; Shekhar, Anantha

doi:10.1016/s0166-4328(98)00132-6

Cited by 175 publications

(149 citation statements)

References 44 publications

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“…These data fit with increasing evidence implicating the CRH system in the modulation of social behavior (Hostetler and Ryabinin, 2013). 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).…”

Section: Discussionsupporting

confidence: 86%

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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Section: Discussionsupporting

confidence: 86%

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

Veenit

Riccio

Sandi

2014

Journal of Psychiatric Research

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“…Ongoing work in our lab conducted in rats also suggests that the CRH system in other regions of the amygdala can influence sleep and arousal. For instance, microinjections of Ucn3 into the basolateral amygdala (BLA) decrease REM (unpublished results), a result consistent with findings that local application of CRH or urocortin, which works at CRH receptor sites into BLA in rats produces dose-dependent increases in anxiety behaviors (Sajdyk et al, 1999). Thus, the amygdala could be an important site for the influence of the CRH system on arousal and sleep.…”

Section: Discussionsupporting

confidence: 79%

Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness

et al. 2008

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Corticotropin releasing hormone (CRH) plays a major role in central nervous system responses to stressors and has been implicated in stress-induced alterations in sleep. In the absence of stressors, CRH contributes to the regulation of spontaneous waking. We examined the effects of CRH and astressin (AST), a non-specific CRH antagonist, on wakefulness and sleep in two mouse strains with differential responsiveness to stress to determine whether CRH might also differentially affect undisturbed sleep and activity. Less reactive C57BL/6J (n=7) and high reactive BALB/cJ (n=7) male mice were implanted with a transmitter for determining sleep via telemetry and with a guide cannula aimed into a lateral ventricle. After recovery from surgery and habituation to handling, ICV microinjections of CRH (0.04, 0.2, and 0.4 μg), AST (0.1, 0.4, and 1.0 μg) or vehicle alone (pyrogenfree saline, 0.2 μl) were administered during the fourth h after lights on and sleep was recorded for the subsequent 8 h. Comparisons of wakefulness and sleep were conducted across conditions and across strains. In C57BL/6J mice, REM was significantly decreased after microinjections of CRH (0.2 μg) and CRH (0.4 μg), and NREM and total sleep were decreased after microinjections of CRH (0.4 μg ). CRH (0.4 μg) and AST did not significantly change wakefulness or sleep. In BALB/cJ mice, CRH (0.4 μg) increased wakefulness and decreased NREM, REM and total sleep. AST decreased active wakefulness and significantly increased REM at the low and high dosages. These findings demonstrate that CRH produces changes in arousal when given to otherwise undisturbed mice. Strain differences in the effects of CRH and AST may be linked to the relative responsiveness of C57BL/6J and BALB/cJ mice to stressors and to underlying differences in the CRH system.

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“…Previously, we reported that daily three injections of Ucn1 into the expand basolateral amygdala (BLA) suppressed SI only transiently, but increased sensitivity to sodium lactate significantly (Sajdyk et al, 1999). Thus, in contrast to the long-lasting anxiety observed following daily five Ucn1 injections, daily three Ucn1 injections suppressed SI time at 30 min postinjection, but this reduction did not persist at postinjection day 2.…”

Section: Experimental Protocolmentioning

confidence: 84%

“…On day 7, the rats received a baseline SI test without injection, and were divided into two groups with comparable levels of baseline SI time. On day 9, one group of rats was injected with a subthreshold dose of Ucn1 (6 fmol/100 nl/30 s/day; determined by considering results of experiment 1 above and Sajdyk et al, 1999), while the second group was injected with vehicle for 5 consecutive days. On injection days 1 and 5, the rats were also placed in the SI test at 30 min postinjection.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Thus, a single injection of 6 fmol of Ucn1 failed to reduce SI acutely, whereas it suppressed SI significantly and persistently following five injections. More interestingly, only the Ucn1 and not vehicle-primed rats exhibited increased behavioral and cardiovascular activation following intravenous sodium lactate infusions (Sajdyk et al, 1999;Rainnie et al, 2004), a response similar to certain subtypes of anxiety disorders such as panic and posttraumatic stress disorders (Cowley and Arana, 1990;Jensen et al, 1997). Given the putative involvement of the BNST in anxiety responses, we hypothesized that acute stimulation of CRF receptors within the BNST will increase anxiety in rats, and repeated stimulation of CRF receptors within the BNST will elicit a persistent and unique profile of anxietylike behaviors.…”

Section: Introductionmentioning

confidence: 98%

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Repeated Stimulation of CRF Receptors in the BNST of Rats Selectively Induces Social but not Panic-Like Anxiety

Lee

Fitz

Johnson

et al. 2008

Neuropsychopharmacol

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Increased extra-hypothalamic corticotrophin-releasing factor (CRF) neurotransmission has been suggested as one putative factor in the pathophysiology of anxiety disorders. We have previously reported that administering repeated subanxiogenic doses (termed 'priming') of the CRF receptor agonist urocortin 1 (Ucn1) into the basolateral amygdala (BLA) of rats elicited long-lasting behavioral changes in social interaction (SI) and elevated plus maze (EPM) tests of anxiety. Although substantial similarity exists, the bed nucleus of the stria terminals (BNST) and the amygdala are thought to play distinct roles in anxiety responses. Rats primed with Ucn1 in the BLA not only demonstrated increased anxiety-like behaviors, but also physiological sensitivity to intravenous sodium lactate infusions, which is seen in subjects with panic or posttraumatic stress disorders, but not social or generalized anxiety disorders. In the present study, we tested if similar priming with subanxiogenic doses of Ucn1 in the BNST of rats will induce either chronic anxiety or sensitivity to sodium lactate. After determining the dose of Ucn1 that is subanxiogenic when injected into the BNST, repeated intra-BNST injections of this subanxiogenic dose of Ucn1 (6 fmol/100 nl) elicited persistent (present even after 4 weeks) anxiety-like responses in the SI but not EPM test. Prior local injection of a CRF receptor antagonist, astressin, into the BNST blocked this effect. Unlike Ucn1 priming in the BLA, rats primed in the BNST showed no cardiovascular changes following lactate infusion. Thus, BNST priming appears to selectively model the pathophysiology of subjects with anxiety syndromes like social anxiety, which are not lactate sensitive.

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Role of corticotropin-releasing factor and urocortin within the basolateral amygdala of rats in anxiety and panic responses

Cited by 175 publications

References 44 publications

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

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

Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness

Repeated Stimulation of CRF Receptors in the BNST of Rats Selectively Induces Social but not Panic-Like Anxiety

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