Shannon L Zandy1,2, Douglas B Matthews1,3, Anthony Miller4, Sayaka Tokunaga4, Charles D Blaha4, Guy Mittleman4,5. 1. Division of Psychology, Nanyang Technological University, Singapore 639798. 2. Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. 3. Department of Psychology, University of Wisconsin - Eau Claire, Eau Claire, WI 54702 USA. 4. Department of Psychology, The University of Memphis, Memphis, TN 38152, USA. 5. Department of Psychological Science, Ball State University, Muncie, IN, 47306.
Abstract
RATIONALE: Alcohol use in adolescence is one of the most significant predictors of alcohol dependence in adulthood, yet the neurochemical mechanisms underlying this heightened vulnerability remain unknown. Whereas research has focused on characterizing adaptations in the mesolimbic dopamine (DA) system following ethanol exposure in adolescence, whether these changes persist into adulthood has yet to be determined. OBJECTIVES: The objective of this study is to investigate the effects of binge-intermittent ethanol administration in adolescence (P30-50) or early adulthood (P60-80) on DA in the nucleus accumbens (NAc) core after an ethanol challenge in adulthood following a period of abstinence. METHODS: Male Sprague Dawley rats (n = 160) were administered intermittent ethanol injections, 1 or 3 g/kg, intraperitoneally (i.p.) every other day for 20 days starting on either P30 or 60. Following an ethanol-free period of either 7, 14, or 28 days, we measured DA efflux following an ethanol challenge (3 g/kg, i.p.) using electrochemical recording electrodes bilaterally implanted into the NAc core. RESULTS: Moderate-dose ethanol administration (1 g/kg, i.p.) during adolescence significantly decreased ethanol-evoked DA release in adulthood at 7 and 14 days, but not 28 days, following pretreatment exposure compared to saline controls. Relative to rats pretreated with ethanol in adulthood, moderate-dose ethanol in adolescence significantly reduced DA efflux at all time points measured. Additionally, adult rats pretreated with high dose ethanol administration (3 g/kg, i.p.) displayed significantly decreased DA compared to adolescents after 28 days of withdrawal. CONCLUSIONS: Binge-intermittent ethanol administration during adolescence may induce age-dependent neuroadaptations in the mesolimbic DA system compared to ethanol-treated adults during protracted ethanol withdrawal.
RATIONALE: Alcohol use in adolescence is one of the most significant predictors of alcohol dependence in adulthood, yet the neurochemical mechanisms underlying this heightened vulnerability remain unknown. Whereas research has focused on characterizing adaptations in the mesolimbic dopamine (DA) system following ethanol exposure in adolescence, whether these changes persist into adulthood has yet to be determined. OBJECTIVES: The objective of this study is to investigate the effects of binge-intermittent ethanol administration in adolescence (P30-50) or early adulthood (P60-80) on DA in the nucleus accumbens (NAc) core after an ethanol challenge in adulthood following a period of abstinence. METHODS: Male Sprague Dawley rats (n = 160) were administered intermittent ethanol injections, 1 or 3 g/kg, intraperitoneally (i.p.) every other day for 20 days starting on either P30 or 60. Following an ethanol-free period of either 7, 14, or 28 days, we measured DA efflux following an ethanol challenge (3 g/kg, i.p.) using electrochemical recording electrodes bilaterally implanted into the NAc core. RESULTS: Moderate-dose ethanol administration (1 g/kg, i.p.) during adolescence significantly decreased ethanol-evoked DA release in adulthood at 7 and 14 days, but not 28 days, following pretreatment exposure compared to saline controls. Relative to rats pretreated with ethanol in adulthood, moderate-dose ethanol in adolescence significantly reduced DA efflux at all time points measured. Additionally, adult rats pretreated with high dose ethanol administration (3 g/kg, i.p.) displayed significantly decreased DA compared to adolescents after 28 days of withdrawal. CONCLUSIONS: Binge-intermittent ethanol administration during adolescence may induce age-dependent neuroadaptations in the mesolimbic DA system compared to ethanol-treated adults during protracted ethanol withdrawal.
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