ISSN:
1432-2072
Keywords:
Key words Allopregnanolone
;
Pregnanolone
;
Neurosteroid
;
Neuroactive steroid
;
Motor behavior
;
Ethanol interaction
;
Benzodiazepine
;
Triazolam
;
Diazepam
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Endogenous pregnane steroids, such as allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α, 5α-P) and pregnanolone (3α-hydroxy-5β-pregnan-20-one; 3α,5β-P), allosterically modulate GABAA receptor function and exhibit behavioral effects similar to benzodiazepines, though acting at a distinct recognition site. Inasmuch as some positive allosteric modulators of GABAA receptor function exhibit profound interactions with ethanol, the effects of 3α,5α-P and 3α,5β-P were compared to those of two benzodiazepines, triazolam and diazepam, on the motor function of mice and rats when administered either alone or in combination with ethanol. All four test compounds exhibited dose-related impairment of motor function in the horizontal wire task in mice and the rotorod task in rats. Ethanol caused a marked enhancement of triazolam- and diazepam-induced motor impairment. In contrast, ethanol enhanced to a lesser extent the motor impairment induced by both neurosteroids in mice and not at all in rats. All four compounds increased ethanol-induced behavioral sleep time in mice, although the benzodiazepines did so at a much smaller fraction of their ataxic doses as compared to the neurosteroids. As one of the undesired side-effects of therapeutic use of benzodiazepines is their interaction with ethanol, development of neuroactive steroids as drugs may offer therapeutic advantages.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002130050809
