TY - JOUR
T1 - Allopregnanolone does not influence ethanol-induced conditioned place preference in DBA/2J mice
AU - Gabriel, Kara I.
AU - Cunningham, Christopher L.
AU - Finn, Deborah A.
N1 - Funding Information:
Acknowledgements The expert technical assistance of Season Long and Michelle Tanchuck in determining whole brain ALLOP levels was greatly appreciated. This research was supported by the National Institute on Alcohol Abuse and Alcoholism (AA07468, AA07702, AA10760, AA13785) and a Merit Review Grant from the Department of Veterans Affairs (to D.A.F.).
Funding Information:
EtOH (20%, v/v in saline) was prepared from a 95% stock solution and administered intraperitoneally (6.25 and 12.5 ml/kg for doses of 1 and 2 g/kg, respectively). ALLOP was custom synthesized by and purchased from Dr. R.H. Purdy (Veterans Medical Research Foundation, San Diego, Calif., USA). ALLOP solutions and finasteride [1,(5α)-Androstan-4-aza-3-one-17β-(N-tert-butyl-carboxamide); Steraloids, Newport, R.I., USA] suspensions were prepared in 20% (w/v) 2-hydroxypropyl-β-cyclodextrin (Sigma, St Louis, Mo., USA); β-cyclodextrin alone has no effect on place conditioning in DBA/2J mice (Finn et al. 1997a). ALLOP and finasteride were stirred daily, with fresh preparations made weekly; and were administered intraperitoneally (10 ml/kg for all doses). Doses were determined from previous research (Finn et al. 1997a, 2000; VanDoren et al. 2000; Palmer et al. 2002).
PY - 2004/10
Y1 - 2004/10
N2 - Rationale: The neurosteroid allopregnanolone (ALLOP; 3α-hydroxy- 5α-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, IP) 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, IP), a 5α-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, IP) 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.
AB - Rationale: The neurosteroid allopregnanolone (ALLOP; 3α-hydroxy- 5α-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, IP) 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, IP), a 5α-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, IP) 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.
KW - Allopregnanolone
KW - DBA/2J
KW - Ethanol
KW - Locomotor activity
KW - Place conditioning
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U2 - 10.1007/s00213-004-1862-2
DO - 10.1007/s00213-004-1862-2
M3 - Article
C2 - 15083256
AN - SCOPUS:3142585854
SN - 0033-3158
VL - 176
SP - 50
EP - 56
JO - Psychopharmacology
JF - Psychopharmacology
IS - 1
ER -