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Relation between alcohol abuse and impulsivity

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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Relation between alcohol abuse and impulsivity

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  1. Relation between alcohol abuse and impulsivity - JayandraChiluwal

  2. 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

  3. 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?

  4. 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.

  5. 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

  6. 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

  7. Delay Discounting Task

  8. Figure 2

  9. Table 2

  10. To summarize • Genetic risk factor for alcoholism may be related in part to impulsivity • Whether high impulsivity causes high alcohol drinking is unknown

  11. 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

  12. 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

  13. 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

  14. Chronic Intermittent Ethanol • 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

  15. 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 144-163) and adults(PND 251-270) • Once per week

  16. 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

  17. 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

  18. DDT • 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

  19. Results

  20. 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.

  21. 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

  22. 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 child-hood and adulthood • Adolescents characterised as impulsive and greater risk takers

  23. 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

  24. Phenotype of Adolescents • Lapses in ability to resist temptation • Sensitivity to rewards and incentives • Making riskier decisions in presence of peers vs alone

  25. Neurobiology of Adolescence

  26. 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

  27. Studies have found greater density of dopamine receptors D1 and D2 in striatum- early adolescences, followed by loss in later stages • May have a relation in sensitivity to rewards • Some hormonal changes as well

  28. Ventral Striatal activity(Galvan et. al.)

  29. 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

  30. 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)

  31. 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

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