Ca. Bowen et al., Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: Effect of ethanol training dose and dosing procedure, J PHARM EXP, 289(1), 1999, pp. 405-411
Citations number
41
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
A number of endogenous steroids exhibit rapid, nongenomic effects on the ce
ntral nervous system and are called neuroactive steroids. The rapid mechani
sms of action include modulation of gamma-aminobutyric acid type A (GABA(A)
) and N-methyl-D-aspartate (NMDA) receptors, which are two receptors implic
ated in the behavioral effects of ethanol. It was hypothesized that neuroac
tive steroids that positively modulate GABA(A) receptors or negatively modu
late NMDA receptors, analogous to the actions of ethanol, would produce dis
criminative stimulus effects similar to ethanol. Two groups of male Long-Ev
ans rats (n = 6-8/group) were trained to discriminate between 1.0 or 2.0 g/
kg ethanol (i.g.) and water (i.g.). The neuroactive steroids allopregnanolo
ne, pregnanolone, epipregnanolone, allotetrahydrodeoxycorticosterone, pregn
anolone sulfate, epipregnanolone sulfate, dehydroepiandrosterone, dehydroep
iandrosterone sulfate, pregnenolone, and pregnenolone sulfate (PS), all adm
inistered i.p., were tested for substitution with acute and cumulative dosi
ng procedures (n = 4-8/steroid). The GABA(A)-positive modulatory steroids a
llopregnanolone, pregnanolone, and allotetrahydrodeoxycorticosterone substi
tuted for ethanol, as did the low-efficacy steroid 3 beta,5 beta-P. GABA(A)
-negative modulators, such as dehydroepiandrosterone sulfate and PS, and al
l of the NMDA modulators tested, including PS, pregnanolone sulfate, and ep
ipregnanolone sulfate, did not substitute for ethanol. These results show t
hat certain endogenously occurring neuroactive steroids produce discriminat
ive stimulus effects similar to those of ethanol.