An investigation of endogenous neuroactive steroid-induced modulation of ethanol's discriminative stimulus effects.
Neuroactive steroids exhibit rapid non-genomic central nervous system activity, including modulation of GABAA and NMDA receptors, two receptors known to mediate the effects of methanol. Neuroactive steroids that modulate GABAA receptors in a manner similar to ethanol were expected to potentiate the discriminative stimulus and/or rate-suppressing effects of ethanol. In contrast, neuroactive steroids that modulate GABAA or NMDA receptors in a manner opposite to ethanol were hypothesized to attenuate the effects of ethanol. Adult male rats were trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) from water (i.g.). Animals were pretreated with subthreshold doses (i.p.) of ethanol and neuroactive steroids and exposed to an acute stressor (n = 5), prior to conducting ethanol cumulative-dosing (i.p.) tests. Only ethanol and 3 beta, 5 beta-P pretreatments potentiated the discriminative stimulus effects of ethanol. None of the six neuroactive steroid manipulations attenuated the effects of ethanol. These results demonstrate that a neuroactive steroid, endogenous in humans, can enhance the interoceptive effects of ethanol.
Bowen
C A
CA
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Purdy
R H
RH
Grant
K A
KA
D000428:Alcohol Drinking / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D001921:Brain / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D011280:Pregnanolone