The overall objectives of this proposal are to determine using animal models, neurobiological factors involved in promoting high alcohol drinking behavior in adolescents and to determine the long range consequences of adolescent alcohol drinking. The hypotheses to be tested are that (1) neurobiological factors associated with excessive alcohol drinking in adults are also present at adolescence and contribute to high alcohol consumption in the young; (2) experience with the rewarding effects of alcohol during adolescence in vulnerable individuals exacerbates these reinforcing actions in adulthood and promotes further excessive alcohol consumption; and (3) chronic alcohol drinking during adolescence produces long-range behavioral consequences in adulthood. These hypotheses will be tested using genetic animal models, i.e., the selectively bred alcohol-preferring P and -nonpreferring NP rats and the high-alcohol drinking HAD and low-alcohol drinking LAD replicate lines. All measurements will be conducted on both male and female animals. The first specific aim will determine if there are differences in the serotonin (5-HT) and dopamine (DA) systems between P and NP rats and between HAD and LAD rats at the age of onset of adolescent alcohol drinking by (a) using HPLC-EC analysis to measure the regional CNS contents of 5-HT, DA and their metabolites in animals at 25 days of age; (b) using membrane preparations from selected CNS regions to determine K/D and B/max values for binding of [3H]8-OH-DPAT to 5-HT/1A sites and [3H]Sulpiride to D2 sites; and (c) autoradiography procedures to determine the densities of 5-HT2 sites (labelled with [3H]Ketanserin) and 5-HT/1A sites in selected CNS subregions. The second specific aim will examine the development of alcohol drinking after weaning (day 22 of age) and if this development can be altered by (a) housing conditions; (b) pharmacological interventions; and (c) taste aversion conditioning. The third specific aim will examine the presence of behavioral factors which might be associated with early onset of alcohol drinking, such as (a) low-dose ethanol stimulation of locomotor activity; (b) difference in sensitivity to high-dose ethanol; (c) rapid development of acute ethanol tolerance; and (d) differences in measures of emotionality and cognitive function (e.g., Plus Maze, Morris Water Maze, etc.) between P and HAD versus NP and LAD rats. The fourth specific aim will examine the long range consequences of adolescent alcohol drinking on adult behaviors (i.e., changes in emotionality and cognitive function, changes in response to the reinforcing and aversive actions of ethanol). These studies with animal models are significant since they will provide important information on (a) neurobiological factors which might contribute to adolescent alcohol drinking; (b) methods which might reduce adolescent alcohol drinking; (c) possible behavioral features associated with adolescent alcohol drinking; and (d) potential long range consequences of adolescent alcohol drinking. Information gained from these animal studies will hopefully provide greater insight into the causes and prevention of adolescent alcohol drinking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010256-05
Application #
2837279
Study Section
Special Emphasis Panel (SRCA (43))
Program Officer
Witt, Ellen
Project Start
1994-12-01
Project End
1999-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
005436803
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
Strother, Wendy N; Lumeng, Lawrence; Li, Ting-Kai et al. (2005) Dopamine and serotonin content in select brain regions of weanling and adult alcohol drinking rat lines. Pharmacol Biochem Behav 80:229-37

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