Alcohol and Adolescence

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Alcohol and Adolescence

• Linda Patia Spear
• Binghamton University
• Edited by
• Susan Tapert
• Univ. of California at San Diego

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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

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

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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

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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

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Adolescent alcohol intake
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Adolescent-Related Alterations in Ethanol
Sensitivity

• Lessened sensitivity to ethanol-induced
• Sedation
• Dysphoria
• Social inhibition
• Motor impairment
• Anxiolytic effects
• Analgesia
• Hangover effects

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Ethanol Sedation
(Silveri Spear, 1998)
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Adolescent-Related Alterations in Ethanol
Sensitivity

• Lessened sensitivity to ethanol-induced
• Sedation
• Dysphoria
• Motor impairment
• Hypothermia
• Social inhibition
• Analgesia
• Hangover effects

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Rate of Ethanol Metabolism
BEC-derived
BrEC-derived
mg/dl/hr
Age
(Silveri Spear, 2000)
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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

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Alcohol and Spatial Learning
Saline
1.0 g/kg EtOH
2.0 g/kg EtOH
Distance Swam to Criterion (cm ? SEM)
Adolescent
Adult
(Markwiese et al., 1998)
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Ethanol-Induced Social Facilitation
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Overall Social Activity
(Varlinskaya Spear, 2001)
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Overall Activity
(Varlinskaya Spear, 2001)
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Familiar Social Situation
Adults

Frequency / 10 min

Dose of Ethanol (g/kg)
(Varlinskaya Spear, 2002)
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Adolescent-Related Alterations in Ethanol
Sensitivity

• Greater sensitivity to ethanol-induced
• Impairment in LTP and spatial water maze
  performance
• Facilitation of social behavior

• Lessened sensitivity to ethanol-induced
• Sedation
• dysphoria
• Social inhibition
• Motor impairment
• Anxiolytic effects
• Analgesia
• Hangover effects

???? opiate NMDA-R function
GABAAR immaturity
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Acute Tolerance
(Mellanby, 1919)
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Acute Tolerance Sedation
(Silveri Spear, 1998)
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Do Human Adolescents Differ from Adults in
Alcohol Sensitivity?

• Increased sensitivity to alcohol-induced
  memory impairment?

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Alcohol effects on performance of
Complex Figures Task
Verbal Learning Test
Total Correct (/- SEM)
(Acheson et al, 1998, Alcoholism Clin.Exp.Res.,
221437-1442.)
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Do Human Adolescents Differ from Adults in
Alcohol Sensitivity?

• Increased sensitivity
• to alcohol-induced memory impairment?
• to alcohol-induced social facilitation?

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Drinking for Social Facilitation

• the literature suggests that most students
  drink for primarily social 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)

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Do Human Adolescents Differ from Adults in
Alcohol Sensitivity?

• Less sensitivity to motor impairing/ intoxicating
  effects?

• Increased sensitivity
• to alcohol-induced memory impairment?
• to alcohol-induced social facilitation?

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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
  adultsubjects were
• We were impressed by how little gross behavioral
  change occurred in the childrenafter a dose
  intoxicating in an adult population.

(Behar et al., 1983)
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Drinks/occasion and use days/month
Female
Male
Average Number
SAMHSA Survey Data (2003)
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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?

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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

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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?

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Lifetime Prevalence of Alcohol Dependence by Age
at First Drink
? Early alcohol use as marker vs. causality?
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Alcohol Withdrawal Spatial Skills

(Tapert Brown,
1999)
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Ethanol-Induced Brain Damage
(Crews et
al., 2000)
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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