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Alcohol and Adolescence

Alcohol and Adolescence. Linda Patia Spear Binghamton University Edited by: Susan Tapert Univ. of California at San Diego. Adolescence. Transition between childhood/immaturity and adulthood/maturity Timing varies (nutrition, gender, genetics, environment)

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Alcohol and Adolescence

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  1. Alcohol and Adolescence Linda Patia Spear Binghamton University Edited by: Susan Tapert Univ. of California at San Diego

  2. Adolescence • Transition between childhood/immaturity and adulthood/maturity • Timing varies (nutrition, gender, genetics, environment) • Soft signs: no events signal onset/offset • Prototypic age ranges: • Humans: 12-18 yrs (early as 8; late as 25) • Rats: 28-42 days (early as 23; late as 55+) • Primates: varies with species (“older juvenile” and early “subadult” stages) • Highly conserved physiological transitions and behavioral characteristics

  3. Physiological Changes During Adolescence Hormonal Body size and Characteristics Neural Alterations Adrenarche (early) adrenal androgens Gonadarche (puberty) LH, FSH, estrogen, testosterone Other GH and stress-induced corticoid release

  4. Gray Matter Maturation (Gogtay et al., 2004, Proc. Natl. Acad. Sci.)

  5. Forebrain Changes in Adolescents • Prefrontal cortex (PFC) • Reduced excitatory drive (humans, primates, rodents) • Decrease in PFC volume (humans & rodents) • Peak of DA innervation (humans, primates, rats) • High DA turnover early followed by decline (rats) • Nucleus accumbens • Low DA turnover early followed by increase (rats) • Hippocampus •  sprouting and myelination (humans, rodents) • Amygdala •  activity (humans, rodents) and PFC connectivity (rodents) • Ventral pallidum / olfactory tubercles •  oxytocin receptor binding (rodents)

  6. Functional Consequences of Adolescent Brain Sculpting • Relationship to hormonal reawakening of puberty? • Support continued cognitive/emotional development • Facilitate highly conserved adolescent behaviors •  social interactions with peers •  risk-taking, novelty-seeking, sensation seeking

  7. Ancillary Consequence of Adolescent Brain Sculpting Altered sensitivity to alcohol/drugs • Multiple neural systems affected by ethanol differ ontogenetically between adolescents and adult • Altering ethanol sensitivity and adaptations • Possibly increasing propensity for use

  8. Adolescent alcohol intake Rats Humans 12 12-20 yrs 10 21 and over Adolescent 12 8 Adult 10 Mean drinks/occasion g/kg EtOH Intake 6 8 6 4 4 2 2 0 0 Male Female Male Female (SAMHSA Survey data, 2003) (Doremus et al. 2005)

  9. Adolescent-Related Alterations in Ethanol Sensitivity: • Lessened sensitivity to ethanol-induced: • Sedation • Dysphoria • Social inhibition • Motor impairment • Anxiolytic effects • Analgesia • Hangover effects

  10. Ethanol Sedation Adults 600 500 400 Adolescents Recovery Time (min ) 300 200 100 0 0 3.5 4.0 4.5 5.0 Dose of Ethanol (g/kg) (Silveri & Spear, 1998)

  11. Adolescent-Related Alterations in Ethanol Sensitivity: Pharmacokinetics? • Lessened sensitivity to ethanol-induced: • Sedation • Dysphoria • Motor impairment • Hypothermia • Social inhibition • Analgesia • Hangover effects

  12. Rate of Ethanol Metabolism 60 50 40 30 20 10 0 P16 P26 P36 P56 P16 P26 P36 P56 BEC-derived BrEC-derived mg/dl/hr Age (Silveri & Spear, 2000)

  13. Adolescent-Related Alterations in Ethanol Sensitivity: • Lessened sensitivity to ethanol-induced: • Sedation • Dysphoria • Social inhibition • Motor impairment • Anxiolytic effects • Analgesia • Hangover effects • Greater sensitivity to ethanol-induced: • Impairment in LTP and spatial water maze performance • Facilitation of social behavior

  14. Alcohol and Spatial Learning 35000 30000 25000 20000 15000 10000 5000 0 Saline 1.0 g/kg EtOH 2.0 g/kg EtOH Distance Swam to Criterion (cm  SEM) Adolescent Adult (Markwiese et al., 1998)

  15. Ethanol-Induced Social Facilitation

  16. Overall Social Activity 120 100 80 Frequency / 10 min 60 40 20 0 0 0.25 0.5 0.75 1 2 3 4 Dose of Ethanol (g/kg) (Varlinskaya & Spear, 2001)

  17. Overall Activity 150 Cotton ball Partner 120 90 Frequency / 10 min 60 30 0 0 0.5 2 3 0 0.5 2 3 Dose of Ethanol (g/kg) (Varlinskaya & Spear, 2001)

  18. Familiar Social Situation Adolescents 100 * 80 60 40 20 0 0 0.25 0.5 0.75 1 0 0.25 0.5 0.75 1 Adults * Frequency / 10 min * Dose of Ethanol (g/kg) (Varlinskaya & Spear, 2002)

  19. Adolescent-Related Alterations in Ethanol Sensitivity: • Lessened sensitivity to ethanol-induced: • Sedation • dysphoria • Social inhibition • Motor impairment • Anxiolytic effects • Analgesia • Hangover effects • Greater sensitivity to ethanol-induced: • Impairment in LTP and spatial water maze performance • Facilitation of social behavior  opiate + NMDA-R function GABAAR immaturity

  20. Acute Tolerance Blood Ethanol Concentration Time (Mellanby, 1919)

  21. Acute Tolerance: Sedation blood 30 brain 25 20 (alcohol level versus dose) 15 Slope of Regression 10 5 0 -5 P16 P26 P36 P46 P56 P96 Postnatal Day (P) (Silveri & Spear, 1998)

  22. Do Human Adolescents Differ from Adults in Alcohol Sensitivity? Increased sensitivity:–to alcohol-induced memory impairment?

  23. Alcohol effects on performance of: 18 13 17 12 16 11 15 14 10 13 9 12 8 11 21-24 yr. 10 25-29 yr. 7 9 6 8 7 5 placebo 0.6 g/kg placebo 0.6 g/kg Complex Figures Task Verbal Learning Test Total Correct (+/- SEM) (Acheson et al, 1998, Alcoholism: Clin.Exp.Res., 22:1437-1442.)

  24. Do Human Adolescents Differ from Adults in Alcohol Sensitivity? • Increased sensitivity: • to alcohol-induced memory impairment? • to alcohol-induced social facilitation?

  25. Drinking for Social Facilitation • “…the literature suggests that most students drink for primarilysocial purposes…” (Berkowitz & Perkins, 1986) • Principle components analysis of HS survey data revealed: “the most important factor across all of the measures of alcohol abuse was drinking for social facilitation” (Beck et al, 1993)

  26. Less sensitivity to motor impairing/ intoxicating effects? Increased sensitivity: to alcohol-induced memory impairment? to alcohol-induced social facilitation? Do Human Adolescents Differ from Adults in Alcohol Sensitivity?

  27. Reduced Alcohol Sensitivity • First intoxicating experience of boys • 8-15 yrs old; 0.5 ml/kg; peak BAC 34-35 mg% • No significant consequences: clinically, subjectively, or on objective test • “…these children exhibited a smaller behavioral change than expected for their BAL” • “None behaved grossly ‘intoxicated’ as our adult…subjects were” • “We were impressed by how little gross behavioral change occurred in the children…after a dose … intoxicating in an adult population.” (Behar et al., 1983)

  28. Drinks/occasion and use days/month 12 12 12-20 12-20 10 10 21 and over 21 and over 8 8 6 6 4 4 2 2 0 0 drinks/occasion days used drinks/occasion days used Male Female Average Number SAMHSA Survey Data (2003)

  29. How Might Adolescent Alcohol Sensitivity Contribute to Problems? • Decreased response to alcohol is a risk factor: • “lower sensitivity to moderate doses of alcohol is associated with a significant increase in the risk of future alcoholism, perhaps through increasing the chances that a person will drink more heavily…” (Schuckit, 1994) • Lowered sensitivity to alcohol seen: • Developmentally: in adolescence • Genetically: in offspring with family history of alcoholism • As function of history/environment: • prior ethanol use (tolerance) • early experience? • stress during adolescence?

  30. How Might Adolescent Alcohol Sensitivity Contribute to Problems? • Alcohol-induced social facilitation may encourage elevated drinking of adolescents Together, may serve as permissive factors to promote high levels of adolescent alcohol use • Yet, adolescents more sensitive to alcohol-induced disruptions in memory and brain

  31. Adverse Effects • Impact on functioning during adolescence: • Greater sensitivity to alcohol-induced disruptions • Memory • Brain plasticity • Mutual synergism: alcohol  risk-taking • Circumvention of normal developmental tasks? • Increased level of stress? • Lasting consequences: • Lasting neurocognitive consequences? • Increased susceptibility to alcohol use disorders?

  32. Lifetime Prevalence of Alcohol Dependence by Age at First Drink 60 Males Females 50 40 % 30 20 10 0 Age at First Drink [Prescott & Kendler (1999) ACER, 23, 101-107] 10 12 14 16 18 20 22 24 26 28 30 Early alcohol use as marker vs. causality?

  33. Alcohol Withdrawal & Spatial Skills (Tapert & Brown, 1999)

  34. Middle Piriform Posterior Piriform Anterior Piriform 800 1000 800 Control 600 600 750 Ethanol 400 400 500 200 200 250 Silver-Stained Area 0 0 0 Adolescent Adult Adolescent Adult Adolescent Adult Olfactory Tubercle Anterior Perirhinal Entorhinal 600 600 4000 3000 400 400 2000 200 200 1000 0 0 0 Adult Adolescent Adult Adolescent Adult Adolescent Ethanol-Induced Brain Damage (Crews et al., 2000)

  35. Summary • Adolescence: • Highly conserved period across species • Numerous brain and behavioral similarities • Adolescents exhibit: • Age-related neural alterations and enhanced acute tolerance associated with: • Less sensitivity to alcohol cues that moderate drinking • Greater sensitivity to ethanol-induced social stimulation and disruption in brain plasticity and memory • Attenuated sensitivity to ethanol effects: • May permit relatively high alcohol intake in adolescence • Potentially lead to adverse consequences during and after adolescence

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