Effects of different ethanol-administration regimes on mRNA and protein levels of steroid 5α-reductase isozymes in prefrontal cortex of adolescent male rats

Underage drinking is a leading public health problem in developed countries. An increasing proportion of adolescents consume alcoholic beverages every weekend. Increased anxiety, irritability, and depression among adolescents may induce them to seek for the anxiolytic and rewarding properties of alcohol. Allopregnanolone (AlloP) shares rewarding effects of ethanol and modulates ethanol intake. The rate-limiting enzyme in the biosynthesis of AlloP is steroid 5 alpha-reductase (5 alpha-R), which is expressed as three isozymes, 5 alpha-R1, 5 alpha-R2, and 5 alpha-R3. The objective of this study was to quantify the expression levels of 5 alpha-R isozymes in prefrontal cortex (PFC) of adolescent male rats after three different regimes of ethanol administration. Adolescent male Wistar rats were administered with ethanol (4 g/kg) or saline intraperitoneally for 1 day (acute), for 7 days (chronic), or every 72 h for 14 days (chronic intermittent). Messenger (m)RNA and protein levels of 5 alpha-R isozymes were measured by quantitative RT-PCR and Western blot, respectively. Ethanol significantly increased mRNA and protein levels of 5 alpha-R1, 5 alpha-R2, and 5 alpha-R3 in the three different regimes of ethanol administration, being higher in the chronic intermittent regime in comparison with the others. The expression of the AlloP-biosynthetic enzyme 5 alpha-Rs increases in the prefrontal cortex of adolescent male rats under acute, chronic, and chronic intermittent regime of ethanol administration. The latter is very interesting because it mimics the teenage drinking behavior.