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Ethanol Self-Administration Pilot Study Emily Koleske 08/03/2016

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Ethanol Self-Administration Pilot StudyEmily Koleske08/03/2016

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Goals of the Study (Background)

• Alcohol is the most commonly used addictive substance in the US

• Excessive alcohol use can lead to neurological impairments and social problems such as alcoholism

• Alcoholism is a progressive and chronic disease

• The goal of this pilot study is to train rats to drink alcohol under a long axis paradigm

• The study will help understand the learning and behavioral mechanisms of addiction and when they stabilize

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Ethanol Task (training)• Rats were given dipper boxes weighing approximately 60-80 g filled

w/10% EtOH solution w/0.1% saccharine

• There is a light delivered when the active lever is pressed

• 20 male Long-Evans rats, aged 6-7 weeks at the beginning of the study

• Each program runs for 180 minutes

• Active infusions, inactive infusions, dipper activations and magazine entries were recorded

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0 20 40 60 80 100 1200

2

4

6

8

10

12

14

16

18

R² = 0.819103478907304

Dippers Earned vs. Weight of EtOH Drunk

Dippers Earned

Wei

ght o

f EtO

H Dr

unk

(g)

Confirming the Correlation between Dippers Earned and EtOH Consumption

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6 7 8 20 2150

55

60

65

70

75

80

85

90

95

69.9

57.9

78.75

88.3

80.4

Dippers earned over Time (days)

Day

Dipp

ers E

arne

d

Dippers Earned after Learning Curve Verses After Three Weeks of Training

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Frank Task• Probabilistic avoidance and reward learning• Combines 3 behaviors together with one task

Train (2 choice)

L1 L2

L4 L5

(30/70) (70/30)

(80/20) (20/80)

Test (novel combinations)

1415

25 24

Choose 1? Avoid 2?

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Primary Goals of the Task• To understand the genetic and neural components that drive decision-

making behavior

• Adaptive learning from positive and negative outcomes

• Multiple roles for dopamine in the brain in reinforcement learning

• It is not known how non-human animals will respond to this task

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Nose-Poke Training• 1 choice, forced-choice training• Rat nose pokes 101 times, gets rewarded for a singular port

only• After two days of 85 trials or more in the specified port, the rat

moves onto the unbiased• Unbiased• Rat is rewarded with a sugar pellet when he chooses any port

(1, 2, 4 or 5)• 201 trials• If the calculated p value is greater than or equal to 0.05 (not

significant) for ports 1 and 2 and ports 4 and 5, he will move on to the 2-choice

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Nose-Poke Training Continued• 2-Choice (Frank Task)• 201 trials• Rat will choose between two portals (1 and 2 or 4 and 5), and will be

rewarded probabilistically

• Test (Probabilistic Selection Task)• 4 ports (1, 2, 4, 5), don’t get reinforced, novel combinations• Choose A, avoid B learning• 201 trials• Test 2 rats get 50% reinforcement

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Predictions for Alcohol Dependence and Probabilistic Learning Task Convergence• Rats formerly trained on the nose-poke tasks will take longer to learn

the alcohol task

• Rats will perform more errors with the behavioral (choose A, avoid B) task after being exposed to alcohol (withdrawal, memory loss, etc.)

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Goals for the Future and Possible Questions• To continue running the programs until we can see a more steady

plateau effect• Train ethanol-dependent animals on the probabilistic learning task• Do a reversal task with the active and inactive levers• Classical conditioning, light cue associated w/pressing of the active

lever, will reinstatement happen if we deprive them of this?• What if we more saccharin? Would the rats drink more? Would we

see correlations?