Adolescents differ from adults in responsivity to a number of ethanol effects. Their insensitivity to the motor incapacitating and sedating effects of ethanol may increase consumption capacities and support higher levels of adolescent drinking, thereby contributing to the unique risks associated with alcohol drinking during adolescence. It has yet to be established whether this unique pattern of alcohol responsivity during adolescence is a function of age-related differences in initial neural sensitivity to alcohol or in the magnitude of tolerance developing within ethanol exposure periods (acute tolerance) or across exposures (rapid and chronic tolerance). There are, however, recent observations of notable ontogenetic alterations in the expression of these ethanol adaptations. Such ontogenetic differences in ethanol tolerance may be particularly pronounced under stressful circumstances, given evidence that vulnerability to stressors may be increased during adolescence and that development of ethanol tolerance is enhanced by stressors. Consequently, the work outlined in this proposal will explore the contribution of tolerance to the unique pattern of alcohol responsivity during adolescence, and the effects of stressors on these adaptational processes. Studies will compare the expression of acute, rapid and chronic tolerance to various characteristic effects of ethanol and the impact of stressors on these ethanol adaptations in male and female, adolescent and adult (as well as weanlings, where feasible) Sprague-Dawley rats. It is predicted that age-related attenuations in sensitivity to specific ethanol effects will be associated with greater acute tolerance but less rapid and chronic tolerance to those effects, with adolescents being particularly vulnerable to stress-induced facilitation of acute, rapid and chronic tolerance. Characterizing the ontogeny of ethanol tolerance and the effects of stressors on these adaptational processes is not only critical for assessing determinants of the unique pattern of alcohol responsivity seen during adolescence, but also may contribute to our understanding of the long-term consequences of adolescent alcohol exposure for later alcohol use and abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AA012525-10
Application #
7485185
Study Section
Special Emphasis Panel (NSS)
Program Officer
Witt, Ellen
Project Start
1999-09-30
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2010-08-31
Support Year
10
Fiscal Year
2008
Total Cost
$297,607
Indirect Cost
Name
State University of NY, Binghamton
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
090189965
City
Binghamton
State
NY
Country
United States
Zip Code
13902
Willey, Amanda Rachel; Anderson, Rachel Ivy; Morales, Melissa et al. (2012) Effects of ethanol administration on corticosterone levels in adolescent and adult rats. Alcohol 46:29-36
Willey, Amanda R; Spear, Linda P (2012) Development of anticipatory 50 kHz USV production to a social stimuli in adolescent and adult male Sprague-Dawley rats. Behav Brain Res 226:613-8
Ramirez, Ruby Liane; Varlinskaya, Elena I; Spear, Linda P (2011) Effect of the selective NMDA NR2B antagonist, ifenprodil, on acute tolerance to ethanol-induced motor impairment in adolescent and adult rats. Alcohol Clin Exp Res 35:1149-59
Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P (2011) Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake. Alcohol Clin Exp Res 35:1392-403
Morales, Melissa; Varlinskaya, Elena I; Spear, Linda P (2011) Age differences in the expression of acute and chronic tolerance to ethanol in male and female rats. Alcohol Clin Exp Res 35:1614-24
Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P (2011) Different chronic ethanol exposure regimens in adolescent and adult male rats: effects on tolerance to ethanol-induced motor impairment. Behav Brain Res 225:358-62
Pautassi, Ricardo Marcos; Myers, Mallory; Spear, Linda Patia et al. (2011) Ethanol induces second-order aversive conditioning in adolescent and adult rats. Alcohol 45:45-55
Varlinskaya, Elena I; Spear, Linda P (2010) Sensitization to social anxiolytic effects of ethanol in adolescent and adult Sprague-Dawley rats after repeated ethanol exposure. Alcohol 44:99-110
Spear, Linda Patia; Varlinskaya, Elena I (2010) Sensitivity to ethanol and other hedonic stimuli in an animal model of adolescence: implications for prevention science? Dev Psychobiol 52:236-43
Doremus-Fitzwater, Tamara L; Spear, Linda P (2010) Age-related differences in amphetamine sensitization: effects of prior drug or stress history on stimulant sensitization in juvenile and adult rats. Pharmacol Biochem Behav 96:198-205

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