Lack of evidence of a role for the neurosteroid allopregnanolone in ethanol-induced reward and c-fos expression in DBA/2 mice.
Previous studies using the 5alpha-reductase inhibitor finasteride suggest that progesterone metabolites, particularly the endogenous neurosteroid allopregnanolone, mediate some of the effects of ethanol. Consequently, we studied the effect of finasteride (2 x 25 mg/kg s.c., 12 h apart) pretreatment on the acquisition and expression of ethanol (2 g/kg i.p.) induced conditioned place preference and c-fos expression in DBA/2 mice; a strain known to be particularly sensitive to ethanol. Ethanol administration induced a clear conditioned place preference and widespread c-fos expression, with elements of the extended amygdala, Edinger-Westphal nucleus and paraventricular nucleus being especially sensitive. However, despite an approximately 99% decrease in whole brain allopregnanolone content, finasteride pretreatment had remarkably little effect on either ethanol-induced conditioned place preference or ethanol-induced c-fos expression. Thus, aside from a general stimulatory effect on c-fos expression in the ventral tegmental area, and generally mild depression of locomotor activity, no other effects of finasteride or interaction with ethanol effects were identifiable. Together, these studies suggest that endogenous allopregnanolone plays little part in mediating acute ethanol-induced reward or neural activation in DBA/2 mice.
Murphy
Niall P
NP
Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wakoshi, Saitama 351-0198, Japan. nmurphy@riken.jp
Sakoori
Kazuto
K
Okabe
Chinami
C
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000009:adverse effects; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D018120:Finasteride / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011280:Pregnanolone / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D000431:Ethanol; D011374:Progesterone; D018120:Finasteride; D011280:Pregnanolone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase