BACKGROUND: Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self-stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward. These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine. METHODS: Male C57 and DBA mice were implanted with unipolar stimulating electrodes in the lateral hypothalamus and conditioned to spin a wheel for reinforcement by the delivery of rewarding electrical stimulation (i.e., brain stimulation-reward or BSR). Using the curve-shift method, the BSR threshold (theta(0)) was determined immediately before and after oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol concentration (BAC) was measured to determine the influence of alcohol metabolism on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0, 30.0 mg/kg) or saline intraperitoneally. RESULTS: In C57 mice, the 0.6 g/kg dose of alcohol lowered BSR thresholds by about 20%, during the rising (up to 40 mg/dl), but not falling, phase of BAC. When given to the DBA mice, alcohol lowered BSR thresholds over the entire dose range; the largest reduction was by about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was more potent in DBA mice than in C57 mice as revealed by a leftward shift in the cocaine dose-response curve. For both alcohol and cocaine, effects on BSR threshold were dissociable from effects on operant response rates. CONCLUSIONS: In C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechanisms of brain reward. The DBA mice are more sensitive to the reward-potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique.
BACKGROUND: Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self-stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward. These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine. METHODS: Male C57 and DBAmice were implanted with unipolar stimulating electrodes in the lateral hypothalamus and conditioned to spin a wheel for reinforcement by the delivery of rewarding electrical stimulation (i.e., brain stimulation-reward or BSR). Using the curve-shift method, the BSR threshold (theta(0)) was determined immediately before and after oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol concentration (BAC) was measured to determine the influence of alcohol metabolism on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0, 30.0 mg/kg) or saline intraperitoneally. RESULTS: In C57 mice, the 0.6 g/kg dose of alcohol lowered BSR thresholds by about 20%, during the rising (up to 40 mg/dl), but not falling, phase of BAC. When given to the DBAmice, alcohol lowered BSR thresholds over the entire dose range; the largest reduction was by about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was more potent in DBAmice than in C57 mice as revealed by a leftward shift in the cocaine dose-response curve. For both alcohol and cocaine, effects on BSR threshold were dissociable from effects on operant response rates. CONCLUSIONS: In C57 and DBAmice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechanisms of brain reward. The DBAmice are more sensitive to the reward-potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique.
Authors: Jason M Wiebelhaus; Travis W Grim; Robert A Owens; Matthew F Lazenka; Laura J Sim-Selley; Rehab A Abdullah; Micah J Niphakis; Robert E Vann; Benjamin F Cravatt; Jenny L Wiley; S Stevens Negus; Aron H Lichtman Journal: J Pharmacol Exp Ther Date: 2014-11-14 Impact factor: 4.030
Authors: Thorfinn T Riday; Eric W Fish; J Elliott Robinson; Thomas M Jarrett; Megan M McGuigan; C J Malanga Journal: Brain Res Date: 2011-11-07 Impact factor: 3.252
Authors: J Elliott Robinson; Abigail E Agoglia; Eric W Fish; Michael C Krouse; C J Malanga Journal: Behav Brain Res Date: 2012-06-21 Impact factor: 3.332
Authors: Irene Morganstern; Guo-Q Chang; Jessica R Barson; Zhiyu Ye; Olga Karatayev; Sarah F Leibowitz Journal: Alcohol Clin Exp Res Date: 2010-03-10 Impact factor: 3.455
Authors: Eric W Fish; J Elliott Robinson; Michael C Krouse; Clyde W Hodge; Cheryl Reed; Tamara J Phillips; C J Malanga Journal: Psychopharmacology (Berl) Date: 2011-10-07 Impact factor: 4.530
Authors: Eric W Fish; Abigail E Agoglia; Michael C Krouse; R Grant Muller; J Elliott Robinson; C J Malanga Journal: Behav Pharmacol Date: 2014-02 Impact factor: 2.293
Authors: A Leslie Morrow; C J Malanga; Eric W Fish; Buddy J Whitman; Jeff F DiBerto; J Elliott Robinson Journal: Psychopharmacology (Berl) Date: 2014-05-09 Impact factor: 4.530
Authors: John F Smiley; Mariko Saito; Cynthia Bleiwas; Kurt Masiello; Babak Ardekani; David N Guilfoyle; Scott Gerum; Donald A Wilson; Csaba Vadasz Journal: Alcohol Date: 2015-07-21 Impact factor: 2.405