Adolescence is a time of considerable transformation in stress-sensitive brain regions that play key roles in the processing of rewarding and social/emotional stimuli and in areas that exert regulatory control over these regions. Given that lasting effects of substances are most likely to occur when systems sensitive to those substances are changing developmentally, we hypothesize that adolescent intermittent ethanol (AIE) exposure will induce lasting effects on social behavior and on the social rewarding and aversive effects of ethanol, leading to persistent elevations in adult intake due in part to alcohol's social anxiolytic properties. Indeed, social rewarding effects of alcohol are critical for the initiation of alcohol use in adolescence and escalation to heavy drinking among individuals with social anxiety, with socially anxious alcoholics showing greater levels of social impairment than non-dependent, socially anxious individuals. The proposed studies will investigate the consequences of voluntary and experimenter-administered adolescent intermittent alcohol (AIE) on later social anxiety and reward, the efficacy of alcohol for countering these lasting perturbations in social behavior, and the impact on later voluntary intake of ethanol, along with neural/genetic adaptations underlying these effects. Using synergisms provided by the NADIA, the proposed research will address the following aims: (1) test whether AIE increases baseline levels of anxiety-like behavior under social circumstances in adulthood and exacerbates stress-induced social anxiety, and determine the efficacy of acute ethanol for reversing this social anxiety;(2) determine whether AIE exposure disrupts the rewarding and/or hedonic value of social stimuli, whether these alterations are further exacerbated by stress, and the efficacy of acute ethanol for reversing these effects;(3) assess whether AIE enhances ethanol drinking in adulthood and decreases sensitivity to the aversive properties of ethanol, and whether these effects of AIE are further exacerbated by social context in adulthood;(4) investigate AIE effects on dopamine transmission during adulthood by measuring real-time dopamine release in nucleus accumbens in response to social stimuli and assessing dopamine-related gene expression in key limbic regions.

Public Health Relevance

The proposed investigations of lasting effects of adolescent alcohol exposure on social anxiety, alcohol's anxiolytic properties, and underiying neural/genetic adaptations are of considerable relevance, given the importance of alcohol's social rewarding properties in initiating use and escalating to heavy drinking among individuals with social anxiety, along with the greater social impairment seen in socially anxious alcoholics.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA019972-05
Application #
8718942
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Regunathan, Soundar
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
State University of NY, Binghamton
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Binghamton
State
NY
Country
United States
Zip Code
13902
Varlinskaya, Elena I; Spear, Linda P (2015) Social consequences of ethanol: Impact of age, stress, and prior history of ethanol exposure. Physiol Behav 148:145-50
Morales, Melissa; Schatz, Kelcie C; Anderson, Rachel I et al. (2014) Conditioned taste aversion to ethanol in a social context: impact of age and sex. Behav Brain Res 261:323-7
McClory, Alexander James; Spear, Linda Patia (2014) Effects of ethanol exposure during adolescence or in adulthood on Pavlovian conditioned approach in Sprague-Dawley rats. Alcohol 48:755-63
Shnitko, Tatiana A; Robinson, Donita L (2014) Anatomical and pharmacological characterization of catecholamine transients in the medial prefrontal cortex evoked by ventral tegmental area stimulation. Synapse 68:131-43
Morales, Melissa; Anderson, Rachel I; Spear, Linda P et al. (2014) Effects of the kappa opioid receptor antagonist, nor-binaltorphimine, on ethanol intake: impact of age and sex. Dev Psychobiol 56:700-12
Broadwater, Margaret A; Spear, Linda P (2014) Tone conditioning potentiates rather than overshadows context fear in adult animals following adolescent ethanol exposure. Dev Psychobiol 56:1150-5
Spear, Linda Patia (2014) Adolescents and alcohol: acute sensitivities, enhanced intake, and later consequences. Neurotoxicol Teratol 41:51-9
Spear, Linda Patia; Swartzwelder, H Scott (2014) Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review. Neurosci Biobehav Rev 45:1-8
Broadwater, Margaret; Spear, Linda P (2014) Consequences of adolescent or adult ethanol exposure on tone and context fear retention: effects of an acute ethanol challenge during conditioning. Alcohol Clin Exp Res 38:1454-60
Varlinskaya, Elena I; Truxell, Eric; Spear, Linda P (2014) Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood. Alcohol 48:433-44

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