The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats

Jutkiewicz, Emily M.; Wood, Susan K.; Houshyar, Hani; Hsin, Ling‐Wei; Rice, Kenner C.; Woods, James H.

doi:10.1007/s00213-005-2164-z

Cited by 80 publications

(59 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 15 min of forced swim has been documented to increase ACTH levels to 200-340 pg/ml, four-to sevenfold above baseline (Jutkiewicz et al, 2005). In the current studies, the 2-h water exposure ACTH had recovered to levels of 143 (711) pg/ml in control rats.…”

Section: Swim Exposure: Acthsupporting

confidence: 45%

“…The dose ranges for CRF antagonists were selected based on previous studies demonstrating antalarmin's (Deak et al, 1999;Webster et al, 1996), R121919's (Heinrichs et al, 2002;Jutkiewicz et al, 2005), and astressin B's (Rivier et al, 2003) ability to inhibit stress-induced release of ACTH. Previous studies have reported active doses of RU486 ranging from 3 (Cook, 2002) to 100 mg/kg (Dal-Zotto et al, 2003).…”

Section: Drug Treatmentsmentioning

confidence: 99%

See 1 more Smart Citation

Facilitation of Cardiac Vagal Activity by CRF-R1 Antagonists during Swim Stress in Rats

Wood

Verhoeven

Savit

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

Exposure to stressors that elicit fear and feelings of hopelessness can cause severe vagal activation leading to bradycardia, syncope, and sudden death. These phenomena though documented, are difficult to diagnose, treat clinically, and prevent. Therefore, an animal model incorporating these cardiovascular conditions could be useful. The present study examined 'sinking' during a 2-h swim stress, a phenomenon that occurs in 50% of rats during 251C water exposure. Concurrent measurements of body temperature, immobility, heart rate (HR), and PR interval (a measure of vagal activity) were made. Neither decreases in immobility nor variations in hypothermia during swim were correlated with sinking. Bradycardia was more severe in sinking rats (average minimum HR7SEM; 143713 vs 247714; po0.01), and PR interval was elevated (po0.0001). To examine potential modulation of vagal activity during stress, corticotropinrelasing factor (CRF) receptor antagonists (antalarmin, R121919 and astressin B), a glucocorticoid receptor antagonist (RU486), and a peripherally acting cholinergic antagonist (methylatropine nitrate) were administered. The centrally acting CRF antagonist, antalarmin (32 mg/kg), produced elongation of the PR interval (po0.0001), robust bradycardia (135718; po0.001), and increased sinking (92%; po0.05), and methylatropine nitrate (3.2 mg/kg) blocked these effects. Corroborating these data, two different CRF antagonists, R121919 (30 mg/kg) and astressin B (intracerebroventricular (i.c.v.), 0.03 mg/rat) increased sinking to 100%. RU486 (20 mg/kg) blocked HPA axis negative feedback and decreased percent sinking to 25%. From these studies, we concluded that sinking during a 2-h water exposure was a result of extreme vagal hyperactivity. Furthermore, stress-induced CRF release may serve to protect against elevated cardiac vagal activity.

show abstract

Section: Swim Exposure: Acthsupporting

confidence: 45%

Section: Drug Treatmentsmentioning

confidence: 99%

Facilitation of Cardiac Vagal Activity by CRF-R1 Antagonists during Swim Stress in Rats

Wood

Verhoeven

Savit

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…High doses of CRF infused into the PVH and BNST produce behavioral inhibition, freezing, aversion and autonomic arousal (Monnikes et al, 1992). There is extensive evidence for enhanced CNS CRF release and action in depression (Berns and Nemeroff, 2003), preclinical studies have shown CRFR1 antagonists to have antidepressant potential (Jutkiewicz et al, 2005;Overstreet et al, 2004). According to the present framework, it would be predicted that CRFR1 antagonists in models of depression would attenuate the fos response of the stress network and restore that of the positive network to a motivational stimulus.…”

Section: Stress Area Activationmentioning

confidence: 90%

A final common pathway for depression? Progress toward a general conceptual framework

Stone

Yang

Quartermain

2008

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

Functional neuroimaging studies of depressed patients have converged with functional brain mapping studies of depressed animals in showing that depression is accompanied by a hypoactivity of brain regions involved in positively motivated behavior together with a hyperactivity in regions involved in stress responses. Both sets of changes are reversed by diverse antidepressant treatments. It has been proposed that this neural pattern underlies the symptoms common to most forms of the depression, which are the loss of positively motivated behavior and increased stress. The paper discusses how this framework can organize diverse findings ranging from effects of monoamine neurotransmitters, cytokines, corticosteroids and neurotrophins on depression. The hypothesis leads to new insights concerning the relationship between the prolonged inactivity of the positive motivational network during a depressive episode and the loss of neurotrophic support, the potential antidepressant action of corticosteroid treatment, and to the key question of whether antidepressants act by inhibiting the activity of the stress network or by enhancing the activity of the positive motivational system. Keywords depression; neuroimaging; fos; final common pathway; cytokines; corticosteroids; monoamines; neurotrophins; theory The quest for a final common pathway has long been goal of research in depression. Famous candidates in this search have included dysregulated brain monoamines (Schildkraut, 1965;

show abstract

“…Positive findings in animal models include a few notable studies. In 2004, Nielsen et al demonstrated that treatment with DMP696 and R121919 reduced forced swim immobility (a genetic model of depression) in mice [146]. Similarly Chaki et al showed that olfactory bulbectomized rats, a putative model of depression, reduced hyperemotionality when treated with R278995 [147].…”

Section: Crf1 Receptor Antagonists In Mood and Anxiety Disordersmentioning

confidence: 99%

HPA Axis Modulation in the Treatment of Mood Disorders

Ozbolt¹,

Nemeroff²

2013

Psychiatric Disorders - New Frontiers in Affective Disorders

View full text Add to dashboard Cite

The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats

Cited by 80 publications

References 39 publications

Facilitation of Cardiac Vagal Activity by CRF-R1 Antagonists during Swim Stress in Rats

Facilitation of Cardiac Vagal Activity by CRF-R1 Antagonists during Swim Stress in Rats

A final common pathway for depression? Progress toward a general conceptual framework

HPA Axis Modulation in the Treatment of Mood Disorders

Contact Info

Product

Resources

About