Alphaxalone, a steroid anesthetic, inhibits the startle-enhancing effects of corticotropin releasing factor, but not strychnine.
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 behaviours, 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.
Swerdlow
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NR
Department of Psychiatry, UCSD School of Medicine, La Jolla 92093-0804.
Britton
K T
KT
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011277:Pregnanediones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D013238:Stereotaxic Techniques; D013331:Strychnine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000777:Anesthetics; D011277:Pregnanediones; D003346:Corticotropin-Releasing Hormone; C006477:alphaxalone; D013331:Strychnine