Transcript Jayandra Chiluwal

Relation between alcohol abuse
and impulsivity
- Jayandra Chiluwal
• Excessive alcohol drinking- third leading cause
of preventable deaths
• Shortens life by 30 years
• High level of alcohol drinking among
adolescents and young adults- major public
health concern
• Impulsivity associated with alcoholism
Grahame et. Al.
• High impulsivity prevalent in drug addicts and
alcoholics vs non addicts
• May be considered as a candidate
endophenotype(measurable, heritable biological state that is
hypothesized to underlie and precede the development of a disorder, and
a presumably closely related to the particular alleles that cause a
disorder)
• Whether impulsivity could be an
endophenotype or result of history of deug
use?
• Drug reward not along with impulsivity results
in addiction.
• Impulsivity - valuing smaller immediate
rewards vs larger delayed rewards.
• Delay discounting task(DDT)- extent to which
time degrades the subjective rewarding value
of the delayed reinforcer.
• Replicated lines of High Alcohol Preferring(HAP)
mice, Low Alcohol Preferring(LAP) and Low
drinking progenitor mice(HS/Lbg) used
• Based on high and low alcohol preference on
free choice between alcohol and water
• Over generations, alleles get concentration in
two opposite directions
• If impulsivity an endophenotype, selection for
high vs low ethanol should be different
Materials and methods
• Parents of HAP1 and HAP2(gen. 34 and 23
respectively) had 84%
• Parents of LAP2(gen 23) – 6%
• HS/Lbg- 15%
• HAP2/LAP2 – 2 cohorts of 24(12m/12f) each
• HAP1/HS/Lbg- 1 cohort of 24
Delay Discounting Task
Figure 2
Table 2
To summarize
• Genetic risk factor for alcoholism may be
related in part to impulsivity
• Whether high impulsivity causes high alcohol
drinking is unknown
Mejia-Toiber et. al.
• Young drinkers(<25)  high impulsivity,
novelty seeking & low harm avoidance
• Anxiety like behavior may be affected by
drinking
• Increased impulsive choice in adult abstinent
alcohlics & heavy drinkers vs light drinkers
• No study on long term effects of binge ethanol
exposure during adolescence/adulthood on
impulsivity
• Neither in anxiety during W or W/o a history
of ethanol exposure
• Aim- To investigate impulsive choice and
anxiety in rats exposed to Chronic Intermittent
Ethanol(CIE) during adolescence/adulthood
Materials and Methods
• Adolescent experimental grouprats born in
lab from pregnant Wistar rats
• Adult experimental group rats aged 134
Post natal days(PND)
• Both from Charles River
• Delay discounting Task
Chronic Intermittent Ethanol
• Adolescent(PND 28-53) and Adult(PND-146171) -> exposed to CIE or water 
Intragastrically(IG)
• 1-5g/kg of 25% (v/v) ethanol 3 times a day on
a 2 day on 2 day off regimen Total seven 2day ons
• Same regimen with sterile water
Acute Saline/Ethanol Challenge
• Acute saline/ethanol(0.5, 1 and 2 g/kg IP) in a
volume of 1ml/kg, 15 minute before session
• During adulthood to adolescents(PND 144163) and adults(PND 251-270)
• Once per week
4-day Binge
• 1-4g/kg of a 25% (v/v) ethanol solution(IG) in sterile
solution twice per day w/ 6-hour interval for 4
days
• Adolescents(PND 181-184) and Adults(PND 271-274)
• Control- sterile water (IG); same regimen
• Blood(200µl) collected(tip of tail) 60-90 min after
ethanol dose
• 2nd, 4th and 6th binge days during CIE, on last injection
of 4-d binge & ethanol challenge after DDT
Light potentiated startle and Acoustic
startle response
• 4 blocks 2 sessions(2 blocks each)
• 1st block (in dark)
- 5 min- undisturbed; 5 min 65 db white
noise(throughout)
- 30 startle stumuli(10 each of 90, 95 and
105 db) in every 30 sec.
• 2nd block same; In dark LPS; In light ASR
DDT
• Immediate reward-1 pellet; delayed reward 4
pellets
• Each session- 5 blocks of 12 trials each(first 2forced then 10-free)
• Reward delay 0, 10, 20, 40 and 60 s for 5
blocks
• Impulsive choice- Choice of large reward for
each delay block per session
Results
A- Significant difference in Large reward choice in Young adults: Saline vs Ethanol
B- No significant
E- # significant less choice of large reward by young adults in higher alcohol conc.
Highlights
• CIE exposure and age had no effect on
baseline impulsive choice
• Ethanol increased impulsivity in younger adult
rats regardless of CIE exposure
• CIE withdrawal-induced decrease in anxiety
and arousal were not age specific
• Subsequent ethanol withdrawal produced
age-dependent increases in anxiety
Neurobiology of Adolescent Brain
and behavior
• Adolescence: Period of development
associated with progressively greater
efficiency of cognitive control capacity.
• Depends upon maturation of Pre frontal
cortex yet different in adolescent from childhood and adulthood
• Adolescents characterised as impulsive and
greater risk takers
Neurobiological model of Adolescence
Model showing development of Ventral striatum and PFC in humans
-Due to earlier maturation of sub cortical projections relative to top-down PFC the
behavior in adolescents is non-linear
Phenotype of Adolescents
• Lapses in ability to resist temptation
• Sensitivity to rewards and incentives
• Making riskier decisions in presence of peers
vs alone
Neurobiology of Adolescence
• Prefrontal cortex involved in cognitive control
• Striatum in detecting and learning about novel
and rewarding cues
• Very early activity of striatum- reward based
associations
• Later development of PFC optomizez greater
gains
• Studies have found greater density of
dopamine receptors D1 and D2 in striatumearly adolescences, followed by loss in later
stages
• May have a relation in sensitivity to rewards
• Some hormonal changes as well
Ventral Striatal activity(Galvan et. al.)
• fMRI confirmed that high risk associated with
Striatum
• Ventral striatum play a role in excitement
• While recent studies show: Impulsivity
inversely correlate with volume of
ventromedial Prefrontal cortex
• Somerville et. al. tested child to adult with
go/no go task(social cues-happy faces) 
adolescent failed to show age-dependent
improvement
• Individuals with less top-down
regulationsusceptible to alcohol and
substance abuse (shown in study based on
populations showing impairments in PFC
before alcohol and drug exposure)
Take home
• Impulsivity may be an endophenotype
• Binge alcohol consumption in early
adolescence may lead to impulsivity
- In adults- anxiety
• Combination of PFC and striatum circuitry has
a role to play
• Some adolescents will be more prone to risky
behavior