Modelling Impulsivity: adapting rodent gambling task (rGT) for the touchscreen box

1. Modelling Impulsivity: adapting rodent gambling task (rGT) for the touchscreen box HaoSheng Sun Mount Sinai School of Medicine

2. Fractionating Impulsivity Winstanley et al., 2010

3. Iowa Gambling Task - IGT • Pathological gambling is a compulsive and maladaptive activity comparable with drug addiction • May be a component of the multi-faceted behavioural construct of “impulsivity”, which includes impulsive action (motor impulsivity), impulsive choice (small immediate reward versus delayed large reward) etc • Iowa Gambling Task was developed to assess and quantify the decision-making defects of neurological patients by simulating real-life decision in conditions of reward and punishment and of uncertainty The optimal strategy is to chose options leading to smaller immediate gains, but also low and infrequent losses C A D B Bechara et al., 1997 Zeeb et al., 2009

4. Iowa Gambling Task - IGT Bechara et al., 1997

5. Impairments on the IGT • Increases in risky decision-making on the IGT are also seen in patients with: • Pathological Gambling (PG) • Substance Abuse Disorder • Parkinson’s Disease patients receiving DA agonist therapy (only a subpopulation) • OCD • Depression

6. Rat Gambling Task - rGT

7. Rat Gambling Task - rGT • 30 min to “gamble” Food Tray Adapted from Fiona Zeeb

8. Rat Gambling Task - rGT • 30 min to “gamble” Food Tray Adapted from Fiona Zeeb

9. Rat Gambling Task - rGT • 30 min to “gamble”     5 sec 5 sec 5 sec 5 sec Premature Premature Premature Food Tray Adapted from Fiona Zeeb

10. Rat Gambling Task - rGT • 30 min to “gamble” Food Tray Adapted from Fiona Zeeb

11. Rat Gambling Task - rGT • 30 min to “gamble” Reward 1 4 2 3 Food Tray Adapted from Fiona Zeeb

12. Rat Gambling Task - rGT • 30 min to “gamble” Reward 1 4 2 3 WIN  Food Tray Adapted from Fiona Zeeb

13. Rat Gambling Task - rGT • 30 min to “gamble” Reward 1 4 2 3 Time-Out 5 40 10 30 LOSS  Food Tray Adapted from Fiona Zeeb

14. Rat Gambling Task - rGT Zeeb et al., 2009

15. Rat Gambling Task - rGT Zeeb et al., 2009

16. Rat Gambling Task - rGT Zeeb et al., 2009

17. Touch Screen Operant Box

18. rGT Training Stage 1 Pre-training Train rats up to criterion (>50 trials in 30 minutes, >80% accuracy, <20% omission) in adapted 4CSRTT with 10 s limited hold and 10 s stimulus durtaion. Stage 2 Forced choice training Present each pellet option (with associated probability of reward and punishment duration) one at a time. 7 sessions. 2 variation of task (VarA: 1 4 2 3 VarB: 4 1 3 2 Stage 3 Free choice training As shown in previous schematics. Continue as same variation of task as before ~30 sessions until stable choice forms

19. rGT Training Sun, unpublished data Zeeb et al., 2009

20. rGT Training Version A: 1 4 2 3 Version B: 4 1 3 2 ?? Sun, Zeeb unpublished data

21. Future Direction • Further validate rGT task in touchscreen boxes • Run animals until stable choice behaviour forms • Validate effect of acute drug treatment on drug behaviour • If difference in baseline behaviour persist, investigate reason for differences (ie housing condition etc) • Effect of viral overexpression of CREB on gambling choice behaviour

22. CREB and impulsive behaviour Sun et al., 2010

23. CREB and impulsive behaviour Investigate whether CREB in the OFC affects other constructs of impulsivity? Ie in the gambling task Sun et al., 2010

24. Acklowdgement Dr.Mark Baxter Dr.Catharine Winstanley Fiona Zeeb And the gambling rats! Terry Echard