Possible Interaction: Ethanol and Finasteride

“We also examined whether finasteride (a 5-α steroid reductase inhibitor), which blocks the synthesis of some neuroactive steroids, reduces the subjective response to alcohol.”

“Early post-natal alterations of NS by administering finasteride induce a decrease in the sensitivity to stimulant effects of low alcohol doses , an increase in alcohol consumption, and a decrease in ventrostriatal dopamine and serotonin levels.”

“In a recent work we reported … the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase … for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that … NS manipulations can increase alcohol abuse vulnerability in adulthood.”

“The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation.”

“ Finasteride (FIN), a 5α-reductase inhibitor that blocks the formation of ALLO and other GABAergic neurosteroids, alters EtOH sensitivity.”

“Recently, we found that Withdrawal Seizure-Prone mice from the first genetic replicate (WSP-1) exhibited behavioral tolerance to the anticonvulsant effect of intrahippocampal ALLO during EtOH withdrawal and that intrahippocampal FIN significantly increased EtOH withdrawal severity.”

“The 5α‐reductase inhibitor finasteride prevented both the increase in the cerebrocortical concentration of 3α,5α‐TH PROG apparent after 4 weeks of ethanol intake and the changes in NPY immunoreactivity and transgene expression induced by ethanol discontinuation.”

“Pretreatment with finasteride increased acute EtOH withdrawal severity in female C57BL/6J and DBA/2J mice but decreased withdrawal severity in male mice of both strains.”

“The 5alpha-reductase inhibitor finasteride can block the formation of ALLO and other GABAergic neurosteroids and also reduce certain effects of EtOH.”

“Treatment with finasteride during chronic EtOH exposure decreased EtOH withdrawal severity and blood EtOH concentrations (BECs), suggesting an additional effect of finasteride on EtOH pharmacokinetics.”

“Moreover, ethanol increased the amplitude of GABA(A) receptor-mediated miniature inhibitory postsynaptic currents recorded from CA1 pyramidal neurones with greater potency in hippocampal slices prepared from socially isolated rats than in those from group-housed rats, an effect inhibited by finasteride.”

“The ability of ethanol to inhibit isoniazid-induced convulsions is greater in isolated rats than in group-housed animals and this effect is prevented by treatment with finasteride.”

“In contrast, pretreatment with finasteride slightly enhanced acute EtOH withdrawal severity in WSP mice, whereas there was no effect of finasteride or EtOH injection on HICs in WSR mice.”

“RESULTS In both chronic EtOH studies, fi asteride pr etreatment reduced EtO H wi thdrawal severity, measured by HICs, and anxiety-related behavior, but only in the WSP selected line.”

“ Ethanol intakes were significantly decreased with acute FIN treatment (days 1-3) and during early withdrawal (days 1-3).”

“Thus, acute FIN treatment modulated ethanol intake patterns in a manner opposite to that previously demonstrated for a physiologically relevant, exogenous ALLO dose, consistent with the ability of a alpha-R inhibitor to block ALLO biosynthesis.”

“Finasteride pretreatment significantly decreased blood EtOH concentration (BEC) upon initiation of withdrawal, suggesting that finasteride may affect withdrawal severity via an alteration in EtOH pharmacokinetics.”

“Pretreatment with finasteride significantly decreased EtOH withdrawal severity only in the female D2 mice, produced a nonselective suppressive effect on HIC in male B6 and D2 mice, and did not significantly alter HIC in female B6 mice.”