CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat

Baldwin, Helen A.; Rassnick, Stefanie; Rivier, Jean; Koob, George F.; Britton, Karen T.

doi:10.1007/bf02244208

Cited by 332 publications

(224 citation statements)

References 18 publications

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“…The EPM test is one of the most widely used non-conditioned tests to evaluate anxiety-like behaviors (Pellow et al, 1985;Baldwin et al, 1991;Rassnick et al, 1991). EPM apparatus consists of two opposite open arms 50 × 10 cm and two opposite arms enclosed by 40 cm high walls and elevated 50 cm from the floor.…”

Section: Elevated Plus-maze (Epm)mentioning

confidence: 99%

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Getachew¹,

Hauser²,

Taylor³

et al. 2008

Pharmacology Biochemistry and Behavior

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Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive-and anxietylike behaviors induced by alcohol were blocked by daily treatment with a tricyclic antidepressant. It may be suggested that prophylactic treatment of alcoholics with an antidepressant prior to detoxification may improve treatment outcome for alcoholism.

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Section: Elevated Plus-maze (Epm)mentioning

confidence: 99%

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Getachew¹,

Hauser²,

Taylor³

et al. 2008

Pharmacology Biochemistry and Behavior

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“…In spite of the evidence suggesting a role of CRF in the ethanol withdrawal syndrome (Ehlers and Chaplin, 1987;Rivier et al, 1990;Baldwin et al, 1991), direct evidence on CRF release in the amygdala during exposure to stress or ethanol withdrawal is still lacking.…”

Section: Department Of Neuropharmacologymentioning

confidence: 99%

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

et al. 1995

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Previous research has suggested a role for corticotropin-releasing factor (CRF) in the anxiogenic effects of stressful stimuli and ethanol withdrawal. This hypothesis was explored in a series of experiments using intracranial microdialysis to monitor CRF-like immunoreactivity (CRF-IR) in the extracellular compartment of the rat amygdala. The synaptic origin of CRF-IR release in the amygdala was determined in vitro by assessing the Ca2+ dependency of 4-aminopyridine stimulated CRF-IR release from tissue preparations of rat amygdala. In vivo experiments were performed in awake rats after the placement of microdialysis probes in the amygdala. In the first experiment, transient restraint stress (20 min) produced an increase of CRF-IR release (basal levels, 1.19 +/- 0.15 fmol/50 microliters; stress levels, 4.54 +/- 1.33 fmol/50 microliters; p < 0.05) that returned to basal values within 1 hr. When 4-aminopyridine (5 mM) was added to the perfusion medium, it consistently increased CRF-IR release (4.83 +/- 0.92 fmol/50 microliters, p < 0.05). In the second experiment, CRF-IR release was measured during ethanol withdrawal in rats previously maintained for 2–3 weeks on a liquid diet containing ethanol (8.5%). Basal CRF-IR levels were 2.10 +/- 0.43 fmol/50 microliters in ethanol exposed rats and 1.30 +/- 0.19 fmol/50 microliters in control rats. During withdrawal, a progressive increase of CRF-IR levels over time was observed, reaching peak values at 10–12 hr after the onset of withdrawal (10.65 +/- 0.49 fmol/50 microliters vs 1.15 +/- 0.30 fmol/50 microliters of control rats, p < 0.01).

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“…administration of CRF increases anxiety-related behaviors in rodents [2,34]. In addition, transgenic mouse lines overexpressing CRF exhibited behavioral states resembling anxiety [24].…”

Section: Introductionmentioning

confidence: 97%

Effects of intra-PAG infusion of ovine CRF on defensive behaviors in Swiss-Webster mice

Carvalho-Netto

Litvin

Nunes-de-Souza

et al. 2007

Behavioural Brain Research

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The midbrain dorsal periaqueductal grey (DPAG) is part of the brain defensive system involved in active defense reactions to threatening stimuli. Corticotrophin releasing factor (CRF) is a peptidergic neurotransmitter that has been strongly implicated in the control of both behavioral and endocrine responses to threat and stress. We investigated the effect of the nonspecific CRF receptor agonist, ovine CRF (oCRF), injected into the DPAG of mice, in two predator-stress situations, the Mouse Defense Test Battery (MDTB), and the Rat Exposure Test (RET). In the MDTB, oCRF weakly modified defensive behaviors in mice confronted by the predator (rat); e.g. it increased avoidance distance when the rat was approached and escape attempts (jump escapes) in forced contact. In the RET, drug infusion enhanced duration in the chamber while reduced tunnel and surface time, and reduced contact with the screen which divides the subject and the predator. oCRF also reduced both frequency and duration of risk assessment (stretch attend posture: SAP) in the tunnel and tended to increase freezing. These findings suggest that patterns of defensiveness in response to low intensity threat (RET) are more sensitive to intra-DPAG oCRF than those triggered by high intensity threats (MDTB). Our data indicate that CRF systems may be functionally involved in unconditioned defenses to a predator, consonant with a role for DPAG CRF systems in the regulation of emotionality.

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CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat

Cited by 332 publications

References 18 publications

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

Effects of intra-PAG infusion of ovine CRF on defensive behaviors in Swiss-Webster mice

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