The overall objectives of this proposal are to determine, using rodent models, neurobiological and behavioral factors involved in promoting high alcohol drinking in adolescent, and some long range consequences of adolescent alcohol drinking. The hypotheses to be tested are (l)-neurobiological and behavioral factors associated with excessive alcohol drinking in adults are also present during adolescence; (2) the acquisition of alcohol drinking during adolescence can be influenced by pharmacological treatments; and (3) chronic alcohol drinking during adolescence produces long-range neurobiological and behavioral consequences in adulthood. These hypotheses will be tested using lines of rats selectively bred for high or low alcohol drinking behavior. Autoradiography procedures, using labeled ligands for the serotonin (5-HT) and dopamine (DA) transporters, will be used to assess differences in adolescent and adult rats with a family history positive (FHP) for alcohol drinking, i.e., alcohol-preferring P and high alcohol-drinking HAD lines, or a family history negative (FHN) for alcohol drinking, i.e., alcohol-nonpreferring NP and low alcohol-drinking LAD rats. Local cerebral glucose utilization (LCGU), as measured by [14C]-2-deoxyglucose (2-DG) uptake and quantitative autoradiography, will be used to determine innate regional differences in functional activity, and the effects of low to moderate doses of ethanol on this activity. Pharmacological challenge studies will examine the response to 5-HT and DA agents in the startle reflex response test. Behavioral studies will be undertaken to evaluate the effects of low to moderate doses of ethanol on prepulse inhibition, and performance on the oscillating bar task. Pharmacological treatment during adolescence with 5-HT3 and opioid antagonists will determine if the acquisition of alcohol drinking can be reduced or prevented in FHP rats. Long-range consequences of adolescent alcohol drinking will be assessed with the ['4 C]-2-DG procedure, and with behavioral measures of spatial navigation Teaming, attention, and motor responses to alcohol. Key findings will be assessed in both male and female rats. Information gained from this proposal will help bridge the gap between human and basic animal research, provide better insight into factors promoting adolescent alcohol drinking, and identify some long-range effects of early alcohol drinking on CNS function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010256-10
Application #
6710010
Study Section
Special Emphasis Panel (ZAA1-EE (02))
Program Officer
Witt, Ellen
Project Start
1994-12-01
Project End
2005-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
10
Fiscal Year
2004
Total Cost
$270,444
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
McBride, William J; Rodd, Zachary A; Bell, Richard L et al. (2014) The alcohol-preferring (P) and high-alcohol-drinking (HAD) rats--animal models of alcoholism. Alcohol 48:209-15
Dhaher, Ronnie; McConnell, Kathleen K; Rodd, Zachary A et al. (2012) Daily patterns of ethanol drinking in adolescent and adult, male and female, high alcohol drinking (HAD) replicate lines of rats. Pharmacol Biochem Behav 102:540-8
Bracken, Amy L; Chambers, R Andrew; Berg, Sarah A et al. (2011) Nicotine exposure during adolescence enhances behavioral sensitivity to nicotine during adulthood in Wistar rats. Pharmacol Biochem Behav 99:87-93
Bell, Richard L; Rodd, Zachary A; Smith, Rebecca J et al. (2011) Modeling binge-like ethanol drinking by peri-adolescent and adult P rats. Pharmacol Biochem Behav 100:90-7
Bell, Richard L; Rodd, Zachary A; Schultz, Jonathon A et al. (2008) Effects of short deprivation and re-exposure intervals on the ethanol drinking behavior of selectively bred high alcohol-consuming rats. Alcohol 42:407-16
Strother, Wendy N; Lumeng, Lawrence; McBride, William J (2008) Acute ethanol effects on local cerebral glucose utilization in select central nervous system regions of adolescent alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. Alcohol Clin Exp Res 32:1875-83
Sable, Helen J K; Bell, Richard L; Rodd, Zachary A et al. (2006) Effects of naltrexone on the acquisition of alcohol intake in male and female periadolescent and adult alcohol-preferring (P) rats. Int J Adolesc Med Health 18:139-49
Bell, Richard L; Rodd, Zachary A; Lumeng, Lawrence et al. (2006) The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addict Biol 11:270-88
Bell, Richard L; Rodd, Zachary A; Sable, Helen J K et al. (2006) Daily patterns of ethanol drinking in peri-adolescent and adult alcohol-preferring (P) rats. Pharmacol Biochem Behav 83:35-46
McBride, William J; Bell, Richard L; Rodd, Zachary A et al. (2005) Adolescent alcohol drinking and its long-range consequences. Studies with animal models. Recent Dev Alcohol 17:123-42

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