Allopregnanolone does not influence ethanol-induced conditioned place preference in DBA/2J mice.
BACKGROUND
The neurosteroid allopregnanolone (ALLOP; 3alpha-hydroxy-5alpha-pregnan-20-one) produces behavioral and discriminative characteristics similar to that of ethanol (EtOH) and can modulate some of the behavioral and electrophysiological effects of EtOH.


OBJECTIVE
The present experiments investigated ALLOP modulation of the effects of EtOH in a place conditioning procedure in male DBA/2J mice.


METHODS
In a series of experiments examining different EtOH doses (1, 2 g/kg) and ALLOP administration times, ALLOP (0, 3.2, 10, 17 mg/kg, i.p.) was administered four times with EtOH prior to placement on a distinctive floor (CS+). On alternate days, vehicle was administered prior to a saline injection paired with the other floor stimulus (CS-). In a separate experiment, finasteride (0, 50, 100 mg/kg, i.p.), a 5alpha-reductase inhibitor that blocks ALLOP synthesis, was administered prior to both CS+ and CS- trials. In a final experiment, animals were place conditioned to EtOH alone, and ALLOP (0, 3.2, 10, 17 mg/kg, i.p.) was administered prior to the preference test only.


RESULTS
During conditioning, ALLOP increased and finasteride decreased EtOH-stimulated activity compared with vehicle pretreatment. Acquisition of 2 g/kg EtOH-induced conditioned place preference was observed in all mice, regardless of treatment with either ALLOP or finasteride. Similarly, ALLOP did not modulate the expression of EtOH-induced place preference. EtOH increased brain ALLOP levels compared with saline; however, ALLOP administration produced dose-dependent elevations in brain ALLOP levels that were not further augmented by EtOH (2 g/kg) administration.


CONCLUSIONS
These findings indicate that ALLOP does not modulate EtOH-induced place conditioning in male DBA/2J mice.
Gabriel
Kara I
KI
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. gabrielk@ohsu.edu
Cunningham
Christopher L
CL
Finn
Deborah A
DA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011280:Pregnanolone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011600:Psychopharmacology / Q000295:instrumentation / Q000379:methods; D013045:Species Specificity; D013997:Time Factors
D000431:Ethanol; D018120:Finasteride; D011280:Pregnanolone