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.
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