Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice.
BACKGROUND
The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of gamma-aminobutyric acid type A (GABA(A)) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects.


OBJECTIVE
The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice.


METHODS
Mice had access to two drinking tubes containing water versus 5% or 10% (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access.


RESULTS
Prior to injection, the 2-h baseline dose of the 10% EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5% EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested).


CONCLUSIONS
ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.
Sinnott
Rachna S
RS
Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University and Department of Veterans Affairs Medical Center, Portland, OR 97201, USA.
Phillips
Tamara J
TJ
Finn
Deborah A
DA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011280:Pregnanolone / Q000494:pharmacology*; D011803:Quinine / Q000008:administration & dosage; D011963:Receptors, GABA-A / Q000187:drug effects; D012439:Saccharin / Q000008:administration & dosage*; D012646:Self Administration; D012737:Sex Factors; D013997:Time Factors
D012739:Gonadal Steroid Hormones; D011963:Receptors, GABA-A; D000431:Ethanol; D011803:Quinine; D011280:Pregnanolone; D012439:Saccharin