alcohol and adolescence linda patia spear binghamton university edited by: susan tapert univ. of...
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Alcohol and AdolescenceAlcohol and Adolescence
Linda Patia SpearBinghamton 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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Physiological ChangesPhysiological Changes During AdolescenceDuring Adolescence
HormonalHormonal Body size and Body size and CharacteristicsCharacteristics
Neural Neural AlterationsAlterations
AdrenarcheAdrenarche(early)(early)
adrenal adrenal androgensandrogens
GonadarcheGonadarche(puberty)(puberty)
LH, FSH,LH, FSH,estrogen,estrogen,
testosteronetestosterone
OtherOtherGH andGH and
stress-inducedstress-inducedcorticoidcorticoid releaserelease
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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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• 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
Functional Consequences of Adolescent Brain Sculpting
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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 intakeM
ean
drin
ks/o
ccas
ion
(SAMHSA Survey data, 2003)
Male Female0
2
4
6
8
10
12
12-20 yrs
21 and over
Humans
Male Female
g/kg
EtO
H I
ntak
e
0
2
4
6
8
10
12 Adult
Adolescent
Rats
(Doremus et al. 2005)
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• Lessened sensitivity to ethanol-induced:– Sedation
– Dysphoria
– Social inhibition
– Motor impairment
– Anxiolytic effects
– Analgesia
– Hangover effects
Adolescent-Related Alterations in Ethanol Sensitivity:
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Ethanol Sedation
5.04.54.03.500
100
200
300
400
500
600
Dose of Ethanol (g/kg)
Rec
over
y T
ime
(min
)
Adults
Adolescents
(Silveri & Spear, 1998)
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• Lessened sensitivity to ethanol-induced:– Sedation
– Dysphoria
– Motor impairment
– Hypothermia
– Social inhibition
– Analgesia
– Hangover effects
Adolescent-Related Alterations in Ethanol Sensitivity:
Pharmacokinetics?
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Rate of Ethanol Metabolism
P16 P26 P36 P560
10
20
30
40
50
60
Age
mg/
dl/h
r
P16 P26 P36 P56
BEC-derived BrEC-derived
(Silveri & Spear, 2000)
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• 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
Adolescent-Related Alterations in Ethanol Sensitivity:
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Alcohol and Spatial Learning
Adolescent Adult
Saline1.0 g/kg EtOH2.0 g/kg EtOH
0
5000
10000
15000
20000
25000
30000
35000
Dis
tanc
e S
wam
to
Crit
erio
n (c
m
SE
M)
(Markwiese et al., 1998)
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Ethanol-Induced Social Facilitation
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0 0.25 0.5 0.75 1 2 3 4
Dose of Ethanol (g/kg)
Fre
qu
ency
/ 1
0 m
in
0
20
40
60
80
100
120
Overall Social Activity
(Varlinskaya & Spear, 2001)
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0 0.5 2 3 0
30
60
90
120
150
Dose of Ethanol (g/kg)
Fre
quen
cy /
10
min
0 0.5 2 3
Partner Cotton ball
Overall Activity
(Varlinskaya & Spear, 2001)
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Familiar Social Situation
0
20
40
60
80
100
Dose of Ethanol (g/kg)
Fre
quen
cy /
10
min
0 0.25 0.5 0.75 1
Adolescents
*
0 0.25 0.5 0.75 1
Adults
*
*
(Varlinskaya & Spear, 2002)
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• 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
Adolescent-Related Alterations in Ethanol Sensitivity:
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Acute Tolerance
Time
Blo
od E
than
ol C
once
ntra
tion
(Mellanby, 1919)
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Acute Tolerance: Sedation
P16 P26 P36 P46 P56 P96
-5
0
5
10
15
20
25
30bloodbrain
Postnatal Day (P)
Slo
pe
of R
eg
ress
ion
(alc
oh
ol l
eve
l ve
rsu
s d
ose
)
(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:
placebo 0.6 g/kg7
8
9
10
11
12
13
14
15
16
17
18T
otal
Cor
rect
(+
/- S
EM
)Complex Figures Task
placebo 0.6 g/kg5
6
7
8
9
10
11
12
13
Verbal Learning Test
21-24 yr.25-29 yr.
(Acheson et al, 1998, Alcoholism: Clin.Exp.Res., 22:1437-1442.)
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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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• Less sensitivity to motor impairing/ intoxicating effects?
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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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)
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Drinks/occasion and use days/month
12-2021 and over
Female
drinks/occasion days used0
2
4
6
8
10
12
Avera
ge N
um
ber 12-20
21 and over
Male
drinks/occasion days used0
2
4
6
8
10
12
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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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
How Might Adolescent Alcohol Sensitivity Contribute to Problems?
• Alcohol-induced social facilitation may encourage elevated drinking of adolescents
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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
0
10
20
30
40
50
60
Age at First Drink
MalesFemales
3028262422201816141210
%
[Prescott & Kendler (1999)ACER, 23, 101-107]
Early alcohol use as marker vs. causality?
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Alcohol Withdrawal & Spatial Skills
(Tapert & Brown, 1999)
30
35
40
45
50
55
60
Treatment (ns)
4-Year Follow-Up(p<.01)
Vis
uo
sp
ati
al T
-sc
ore
Good treatmentoutcome(n=32)
Post-txwithdrawal(n=48)
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Ethanol-Induced Brain Damage
(Crews et al., 2000)
Silv
er-S
tain
ed
Are
a
Adolescent Adult0
200
400
600
800Anterior Piriform
0
200
400
600
Adolescent Adult
Olfactory Tubercle
Adolescent Adult0
250
500
750
1000
Middle Piriform
ControlEthanol
Adolescent Adult0
200
400
600
800Posterior Piriform
Adolescent Adult 0
200
400
600
Anterior Perirhinal
Adolescent Adult0
1000
2000
3000
4000
Entorhinal
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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