Pregnane steroid alphaxalone attenuates anxiogenic behavioral effects of corticotropin releasing factor and stress

Britton, Karen T.; McLeod, Sarah; Koob, George F.; Hauger, Richard L.

doi:10.1016/0091-3057(92)90117-x

Cited by 45 publications

(12 citation statements)

References 28 publications

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“…Higher doses of this neuroactive steroid could not be given in the acute protocol because of its sedative effects. The dose of 3 mg/kg used in the acute study was at the low end of doses reported by others to have anxiolytic effects (Britton et al, , 1992. Another factor is the possibility that rats may have been hyposensitive to the effects of alphaxalone, as has been reported by Cagetti et al (2003), who used a different protocol of ethanol exposure.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Ethanol Withdrawal???Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/??-Aminobutyric Acid Ligands

Knapp

Overstreet

Breese

2005

Alcoholism: Clinical & Experimental Research

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Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals.

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Section: Discussionmentioning

confidence: 99%

Modulation of Ethanol Withdrawal???Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/??-Aminobutyric Acid Ligands

Knapp

Overstreet

Breese

2005

Alcoholism: Clinical & Experimental Research

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“…The most potent neurosteroid modulators of the GABA A receptor complex are allopregnanolone, a metabolite of progesterone, Purdy et al 1991;Twyman and MacDonald 1992) and a synthetic neurosteroid alphaxalone (Harrison et al 1986;Morrow et al 1987). Like alcohol, allopregnanolone has been shown to be anesthetic, (Selye 1942;Kavaliers and Wiebe 1987;Frye andDuncan 1994), anti-convulsant (DeVaud et al 1996;Gasior et al 1997;Kokate et al 1999), sedative (Vanover et al 1999), and to exert anxiolytic-like effects Britton et al 1992;Bitran et al 1993;Zimmerberg et al 1994;Vivian et al 1997;Fish et al 2000).…”

Section: Introductionmentioning

confidence: 96%

Alcohol, allopregnanolone and aggression in mice

et al. 2000

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“…The present study tested the ability of a-helical CRF9-41 administered centrally and the anxiolytic compounds chlordiazepoxide and alphaxalone administered peripherally prior to a restraint stressor to attenuate the suppression of exploratory behavior on the elevated plus-maze. Forced swimming at ambient water temperatures is a stressor that activates the hypothalamo-pituitary-adrenal axis and produces an anxiogenic-like behavioral response on the plus-maze (Britton et al 1992). Although this physiological and behavioral profile is shared with restraint, the swim stressor requires bodily exertion, whereas restraint stress in contrast is designed to limit movement.…”

mentioning

confidence: 99%

Anti-Stress Action of a Corticotropin-Releasing Factor Antagonist on Behavioral Reactivity to Stressors of Varying Type and Intensity

Heinrichs

Menzaghi

Pich

et al. 1994

Neuropsychopharmacol

135

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Central administration of a Corticotropin-Releasing Factor (CRF) antagonist is well documented to attenuate a variety of behavioral responses to several distinct stressors; however, it is not yet clear whether the activation of CRF neurons is dependent on the type or intensity of the experimental stressor, or rather on the particular behavioral response to stress under study. To test the generality of the stress-protective effect of the CRF antagonist, alpha-helical CRF9-41, (1, 5 or 25 micrograms intracerebroventricularly), the present experiments employed a sensitive index of anxiogenic-like behavior by measuring suppression in exploration on the elevated plus-maze following exposure to social, swim, or restraint stressors. A 1 but not 5 or 25 micrograms dose of the CRF antagonist administered just prior to social, swim, or restraint stress reversed the stress-induced inhibition of exploratory behavior. Chlordiazepoxide and the steroid anesthetic, alphaxalone, also attenuated the anxiogenic-like effect of restraint stress and elevated the baseline exploratory behavior of nonstressed control groups. Although the stressors produced a graded secretion of adrenocorticotropin (ACTH) with the ranking restraint > swim > social, the relative amplitude of behavioral reactivity to social, swim, and restraint stress was comparable. The relative efficacy of the CRF antagonist to reverse the stressor effects was also comparable. These results suggest that antagonism of activated brain CRF systems attenuates the behavioral response to stress regardless of the type or intensity of the stressor as measured by ACTH secretion.

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Pregnane steroid alphaxalone attenuates anxiogenic behavioral effects of corticotropin releasing factor and stress

Cited by 45 publications

References 28 publications

Modulation of Ethanol Withdrawal???Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/??-Aminobutyric Acid Ligands

Modulation of Ethanol Withdrawal???Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/??-Aminobutyric Acid Ligands

Alcohol, allopregnanolone and aggression in mice

Anti-Stress Action of a Corticotropin-Releasing Factor Antagonist on Behavioral Reactivity to Stressors of Varying Type and Intensity

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