Presentation on theme: "MODELING MECHANISMS OF FEAR AND ANXIETY: NICOTINE WITHDRAWAL"— Presentation transcript:
1MODELING MECHANISMS OF FEAR AND ANXIETY: NICOTINE WITHDRAWAL AND STRAIN DIFFERENCESMarissa Applegate, Shruthi Deivasigamani, Conor Driscoll, Sumeet Jain, Sarah McAlister, Jacquelyn Olwell, Ravi Pancholi, Claire Rhee, David Gabriel Rissman, Adam Rosenstein, Madison Taormina, Justin ZhangAdvisors: Dr. Graham Cousens and Zack Vogel
2Fear vs. Anxiety Fear Anxiety Directed at a stimulus Dissipates after stimulus is removedConstruct: Phasic FearGeneral uneasinessLong lastingConstruct: Sustained Fear
3Acoustic Startle Response AuditoryInputPNCChange order of animationsMotor Output
4Paradigms of Fear and Anxiety Phasic FearCentral NucleusAnxietySustained FearBed Nucleus of Stria Terminalis (BNST)
5Acoustic Startle Response AmygdalaLateralNucleusCentralNucleusBNSTGet rid of cochlear and spinal. Text smallerPut it in an ovalPNCInput to PNC to Motor OutputMotor OutputAuditoryInputPNC
6Road MapExperiment 1: Effects of Strain Differences on the Light Enhanced Startle Response in Lewis and Sprague- Dawley RatsExperiment 2: Effects of Nicotine Withdrawal on Discrete Cue and Contextual Conditioned FearExperiment 3: Nicotine Withdrawal-Induced Anxiety in the Elevated Zero MazeMAKE MORE EXCITING!!!!!!
7Effects of Strain Differences on the Light Enhanced Experiment 1Effects of Strain Differences on the Light EnhancedStartle Response in Lewis and Sprague-Dawley RatsEvaluate genetic differencesMeasure baseline startle response (1,3)Light-enhanced startle (LES) (2,4,5)Impact on future researchHypotheses – Lewis vs. Sprague-DawleyGreater baseline startleGreater percent increase of LES startle responseSustained fear present after LESChange last hypothesisOr prove it.
8Subjects Experiment 1 Lewis Rat H51-58 8 male Sprague-Dawley Rat H59-H656 male
11Baseline Response Experiment 1 The Lewis rats had a higher baseline startle response when compared to the Sprague-Dawleys.
12Percent Baseline Startle at 95 dB Experiment 1Percent Baseline Startle at 95 dBAt the 95 dB level, the Sprague Dawley rats exhibited a higher LES startle response, and a greater percent increase in startle. The Sprague-Dawley also exhibited a sustained fear.
13Percent Baseline Startle at 105 dB Experiment 1Percent Baseline Startle at 105 dBAt the 105 dB level, the Sprague-Dawley rats still exhibited a higher LES reaction and a greater percent increase.
14Why research withdrawal? 43.5% try to quit smokingOf those, between 70% and 90% fail (6)Connection between nicotine withdrawal and anxietyTreatments to limit withdrawal effects
15Effects of Nicotine Withdrawal on Contextual Conditioned Fear Experiment 2Effects of Nicotine Withdrawal onDiscrete Cue andContextual Conditioned FearLink between withdrawal and sustained fearWithdrawal and Phasic FearHypothesisThere will be no effecton phasic fear.
17Subjects Experiment 2 + 3 .50 .25 .00 Sprague-Dawley Rat H1, H2, H3, H8, H95 maleHigh Dosage of Nicotine (.5mg/kg)Sprague-Dawley RatH4, H11, H12, H13, H145 maleLow Dosage of Nicotine (.25mg/kg)Sprague-Dawley RatH5, H6, H7, H104 maleControl (Saline).50.25.00Injected every day for three weeksTested two hours after injection
20Experiment 2ResultsConclusion: Robust contextual fear potentiated startle with no difference between groups
21Experiment 2ResultsConclusion: No olfactory fear potentiated startle in all groups
22Nicotine Withdrawal-Induced Anxiety in the Elevated Zero Maze Experiment 3Nicotine Withdrawal-InducedAnxiety in the Elevated Zero MazeElevated zero-mazeNicotine withdrawal leads to anxietyElevated zero-maze because rats are afraid of heights; control rats = less anxious… more time in open sections of zero-maze; as anxiety increases, locomotor activity decreases because the rats would be averse to any environmental changesHypothesis: As nicotine dosage increases and causes a higher withdrawal affect, anxiety, locomotor activity, and time spent in the closed sections of the maze will increase.
23Zero Maze Locomotor Activity Experiment 3 Time Spent in Open and Closed AreasWalledLocomotorActivity
24Nicotine Withdrawal-Induced Anxiety in the Elevated Zero Maze Experiment 3Nicotine Withdrawal-InducedAnxiety in the Elevated Zero MazeNicotine Injections2 hour waiting period15 minute testing periodRat placed in maze
25Experiment 3ResultsNicotine dosage had no effect on the amount of time the rats spent in the open sections of the maze.Nicotine dosage had no effect locomotor activity.
26Time in Open vs. Time of Day Experiment 3Time in Open vs. Time of Day
27Conclusion Surprising Data Need more conclusive data Future experiments
28Acknowledgements Dr. Graham Cousens , who is getting married today! Dr. Miyamoto, our fearless leaderMyrna Papier, our indispensible organizerZack Vogel, our epic counselorAll the NJGSS StaffAnd our gracious benefactors:John and Laura OverdeckBayer HealthcareThe Crimmins Family Charitable FoundationNJGSS Alumni and Parents 1984 – 2011Bristol-Meyer SquibbRocheKinder MorganBain Capital Childrens CharityGlastoSmithKlineNovartis
29Reference Sources Laura Overdeck Bayer 1. Ramos A, Kangerski AL, Basso PF, Da Silva Santos JE, Assreuy J, Vendruscolo LF, Takahashi RN. Evaluation of Lewis and SHR rat strains as a genetic model for the study of anxiety and pain. Behavioral Brain Research Feb; [Internet]. [cited 2011 Jul 27] 129(1-2): Available from:2. Steiner MA, Lecourt H, Rakotoariniaina A, Jenck F. Favoured genetic background for testing anxiolytics in the fear-potentiated and light-enhanced startle paradigms in the rat. Behavioural Brain Research Aug; [Internet]. [cited 2011 Jul 27] 221(1): Available from:3. Freet CS, Tesche JD, Tompers DM, Riegel KE, Grigson PS. Lewis rats are more sensitive than Fischer rats to successive negative contrast, but less sensitive to the anxiolytic and appetite-stimulating effects of chlordiazepoxide. Pharmacology, Biochemistry, and Behavior Oct; [Internet]. [cited 2011 Jul 27] 85(2): Available from:4. Davis M, Walker DL, Miles L, Grillon C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology Jan; [Internet]. [cited 2011 Jul 27] 35(1): Available from:5. Jonkman S, Risbrough VB, Geyer MA, Markou A. Spontaneous nicotine withdrawal potentiates the effects of stress in rats. Neuropsychopharmacology Aug; [Internet]. [cited 2011 Jul 27] 33(9): Available from:6. (Bronars C, Saul J. Increasing Reach of Tobacco Cessation Quitlines: A Review of the Literature and Promising Practices [home page on the Internet]. Phoenix (AZ): North American Quitline Consortium; [Introduction; cited 2011 July 27]. 18 p. Available from:Laura OverdeckBayer