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Alphaxalone, a steroid anesthetic, inhibits the startle-enhancing effects of corticotropin releasing factor, but not strychnine

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Abstract

Corticotropin releasing factor (CRF) is a 41 amino acid peptide implicated in the expression of stress-and fear-enhanced behaviors. CRF potentiates the amplitude of the startle reflex, and this effect is reversed by benzodiazepines (BDZ), suggesting that the startle-enhancing effects of CRF are modulated by changes in the GABA/BDZ receptor complex. In the present study, CRF-potentiated startle is inhibited by alphaxalone, a pregnane steroid anesthetic that is thought to act via the GABA/BDZ receptor complex. Alphaxalone (ALX) does not reduce CRF-potentiated startle by producing a generalized reduction in reactivity, since blockade of CRF-stimulated startle was not accompanied by an ALX-induced reduction in baseline startle amplitude, and ALX does not reduce strychnine-potentiated startle. The effects of alphaxalone on CRF-potentiated startle may not be generalized to all CRF-stimulated behaviors, since alphaxalone failed to disrupt CRF-stimulated locomotor activity. CRF-potentiated startle is a useful assay for studying the effects of novel anxiolytic agents, and alphaxalone appears to be a steroid anesthetic with anxiolytic properties in this assay.

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  1. Department of Psychiatry, UCSD School of Medicine, 92093-0804, La Jolla, CA, USA

    Neal R. Swerdlow & Karen T. Britton

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  1. Neal R. Swerdlow
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  2. Karen T. Britton
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Swerdlow, N.R., Britton, K.T. Alphaxalone, a steroid anesthetic, inhibits the startle-enhancing effects of corticotropin releasing factor, but not strychnine. Psychopharmacology 115, 141–146 (1994). https://doi.org/10.1007/BF02244764

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  • DOI: https://doi.org/10.1007/BF02244764

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