Relation between alcohol abuse and impulsivity
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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

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Grahame et al
Grahame et. Al. preventable deaths

  • 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?

  • 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
Materials and methods Alcohol Preferring(LAP) and Low drinking progenitor mice(HS/Lbg) used

  • 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
Delay Discounting Task Alcohol Preferring(LAP) and Low drinking progenitor mice(HS/Lbg) used

Figure 2
Figure 2 Alcohol Preferring(LAP) and Low drinking progenitor mice(HS/Lbg) used

Table 2
Table 2 Alcohol Preferring(LAP) and Low drinking progenitor mice(HS/Lbg) used

To summarize
To summarize Alcohol Preferring(LAP) and Low drinking progenitor mice(HS/Lbg) used

  • 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
Mejia-Toiber et. al. Alcohol Preferring(LAP) and Low drinking progenitor mice(HS/Lbg) used

  • 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 methods1
Materials and Methods during adolescence/adulthood on impulsivity

  • 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
Chronic Intermittent Ethanol during adolescence/adulthood on impulsivity

  • Adolescent(PND 28-53) and Adult(PND-146-171) -> 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 2-day ons

  • Same regimen with sterile water

Acute saline ethanol challenge
Acute Saline/Ethanol Challenge during adolescence/adulthood on impulsivity

  • 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 144-163) and adults(PND 251-270)

  • Once per week

4 day binge
4-day Binge during adolescence/adulthood on impulsivity

  • 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
Light potentiated startle and Acoustic startle response during adolescence/adulthood on impulsivity

  • 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 during adolescence/adulthood on impulsivity

  • Immediate reward-1 pellet; delayed reward 4 pellets

  • Each session- 5 blocks of 12 trials each(first 2-forced 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 during adolescence/adulthood on impulsivity

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 adults: Saline vs Ethanol

  • 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
Neurobiology of Adolescent Brain and behavior adults: Saline vs Ethanol

  • 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 child-hood and adulthood

  • Adolescents characterised as impulsive and greater risk takers

Neurobiological model of adolescence
Neurobiological model of Adolescence adults: Saline vs Ethanol

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
Phenotype of Adolescents adults: Saline vs Ethanol

  • Lapses in ability to resist temptation

  • Sensitivity to rewards and incentives

  • Making riskier decisions in presence of peers vs alone

Neurobiology of adolescence
Neurobiology of Adolescence adults: Saline vs Ethanol

  • Prefrontal cortex involved in cognitive control adults: Saline vs Ethanol

  • 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

Ventral striatal activity galvan et al
Ventral Striatal activity(Galvan et. al.) and D2 in striatum- early adolescences, followed by loss in later stages

  • fMRI confirmed that high risk associated with Striatum and D2 in striatum- early adolescences, followed by loss in later stages

  • 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 and D2 in striatum- early adolescences, followed by loss in later stages susceptible to alcohol and substance abuse (shown in study based on populations showing impairments in PFC before alcohol and drug exposure)

Take home
Take home and D2 in striatum- early adolescences, followed by loss in later stages

  • 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