Ditch the Reliever, Bring on the Fever Duration of sickness behaviour will be significantly different with no aspirin treatment versus aspirin treatment in male rats Alisha Jiwani, Dorcas Kwan, Amanda Li, Joy Santiago
May 10, 2015
Ditch the Reliever, Bring on the Fever
Duration of sickness behaviour will be significantly different with no aspirin
treatment versus aspirin treatment in male rats
Alisha Jiwani, Dorcas Kwan, Amanda Li, Joy Santiago
OutlineIntroduction
What’s the deal with fever and sickness behaviour?
Hypotheses
MethodExperimental PhasesData Analysis
Limitations
Conclusion Implications Applications
Fever
Elevated temperature above the normal range
1800s Anti-pyretics
Fever therapy
What’s the deal with fever and sickness behaviour?
Julius Wagner-Jauregg
“Fever Phobia”
“Fever had become a harmful by-product of infection rather than a host-defense response, probably due to the misconstruction of the relief felt after the use of anti-pyretics, which are often analgesics as well.”
Transformation
Sickness Behaviour
Sickness BehaviourFatigueLoss of appetite Inability to concentrateLoss of interest in social
activity
Adaptive strategyReset priorities
What has been done so far…
Quantitative relationship between cytokine levels of non-specific sickness behaviour symptoms
More research on sickness behaviour
Effect of anti-pyretics in duration of sickness behaviour
Is recovery faster when fever is not suppressed?
We hypothesize…Alternative Hypothesis (H1):There will be a significant difference
in duration of sickness behaviour when antipyretics are administered.
Null Hypothesis (H0):There will be no significant difference
in duration of sickness behaviour when antipyretics are administered.
Method
Albino Wistar Rats
60 Adult male albino rats
200-250 g
Decreased appetite
Decreased activity levels
Increased sleeping time
Groups
Experimental Phases
Phase 1Weeks 1 and 2
Temperature Telemetry Transmitter (TTT) transplant
Recovery (week 1)
Acclimation to device (week 2)
Phase 2Week 3
Measure baselines:
TemperatureFood ConsumptionMotor ActivitySleeping
Behaviour
Phase 3Experimental Day – Induce Fever
Inject Lipopolysaccharide (LPS) for both Aspirin and Non-Aspirin groups
Phase 4Experimental Day – Induce
Treatment
Aspirin group Inject Aspirin at 6-hour
peak of LPS effectWait 2 hours for peak of
Aspirin’s anti-pyretic effect
Non-Aspirin group Inject tragacanth at 6-
hour peak of LPS effect,Wait 2 hours
Phase 5Experimental Day – Data collection
Temperatures
Feeding behaviour (How much food eaten?)
Exploration behaviour (How much activity?)
Sleeping behaviour (How much sleep?)
** each experiment will span over 4 days
Food Consumption
At 24 hr intervals
Remaining food measured on triple beam balance
Food ConsumptionEXPECTED
RESULTS: After fever induction,
initial decrease in appetite for both groups
Animals in Non-Aspirin group will have appetites restored sooner than animals in Aspirin group
Motor ActivityOpen Field Test
Field is separated into 16 boxes, marked by horizontal and vertical blue lines
Camera-based computer tracking system and video camcorder
Total Motor Activity = Line Crossing + Rearing
Motor Activity
EXPECTED RESULTS:The Non-aspirin group
will resume activity sooner over the four days that the Aspirin group
Sleeping Behaviour
Measure duration of sleep in percentage
Measure by camera recording
Sleeping Behaviour
EXPECTED RESULTS: Compared with
baseline: An increase in sleep duration after the LPS injection
Duration of sickness behaviour: the rats with Aspirin injection will experience a longer duration of sickness behaviour
Aspirin
Non-Aspirin
Data Analysis Dependent Paired T-test
Independent variables: Rats with Aspirin vs. Rats with tragacanth
Dependent variables for each experiment: Experiment 1: Remaining food after 24 h (g) Experiment 2: Motor activity calculated Experiment 3: Sleep duration (%)
For each experiment, the dependent variables will be: i. Comparing the baseline level with the performance after
LPS injection ii. Comparing the difference between the 2 groups over the
four-days
Discussion
Limitations
Administration of LPS will always induce fever
Future implications and potential applications
But remember…Take with a grain of
salt
Fever can be fatalToo highFever persists
Appreciation of evolved physiological and psychological mechanisms
Thank you!Dr. Faure, Brandon &
class!
Questions?
ReferencesBrown, R, E., Gunn, R, K., Schellinck, H, M., Wong, A, A., & O’Leary, T, P. (2004) Anxiety, exploratory behaviour, and motor activity in 13 strains of mice. MPD:94. Mouse
Phenome Database website, The Jackson Laboratory, Bar Harbour, Maine USA. http://www.jax.org/phenome. Available March 2008
Camus, P., Lombard, J., Perrichon, M., Piard, F., Gutrin, J. Thivolet, F. B., Jeannin, L. (1989). Bronchiolitis obliterans organising pneumonia in patients taking acebutolol or amiodarone. Thorax, 44, 711-715.
Clement, J. G., Mills, P., Brockway, B. (1989). Use of telemetry to record body temperature and activity in mice. Journal of Pharmacological Methods Viewpoint, 21, 129-140.
Ennaceur, A., Michalikova, S., & Chazot, P, L. (2006). Models of anxiety: Responses of rats to novelty in an open space and an enclosed space. Behavioural Brain Research, 171, 26-49.
Johnnson, R. W. (2002). The concept of sickness behaviour: a brief chronological account of four key discoveries. Veterinary Immunology and Immunopathology, 87, 443-450.
Kelley, K. W., Bluthe, R., Dantzer, R., Zhou, J., Shen, W., Johnson, R. W., Broussarda, S. R. (2003). Cytokine-induced sickness behavior. Brain, Behaviour and Immunity, 17, 112-118.
Kent, S., Buth, R., Kelley, K., Dantzer, R. (1992). Sickness behavior as a new target for drug development. Viewpoint, 13, 24-28.
Kluger, M., Kozak, W., Corm, C., Leon, L. R., Soszynski, D. (1996). The Adaptive Value of Fever. Infectious Disease Clinics of North America, 10 (1), 1-20.
Kozak, W., Conn, C.A., & Kluger, M.J. (1994). Lipopolysaccharide induces fever and depresses
locomotor activity in unrestrained mice. American Journal of Physiology, 266(1), R125-135.
Loux, J.J., DePalma, P.D., & Yankell, S.,L. (1971). Antipyretic testing of aspirin in rats.
Toxicology & Applied Pharmacology, 22(4), 672-675.
Mackowiak, P. A. (2000). Brief History of Antipyretic Therapy. Clinical Infectious Diseases, 31, 154-156.
Makela, M. J., Puhakka, T., Ruuskanen, O., Leinonen, M., Saikku, P., Kimpima, M., Blomqvist, S., Hyppia, T., Arstila, P. (1998). Viruses and Bacteria in the Etiology of the Common Cold. Journal of Clinical Microbiology, 36, 539-542.
Moran, M, M., Roy, R, R., Wade, C, E., Corbin, B, J., & Grindeland, R, E. (1998). Size constraints of telemeters in rats. J Appl Physiol, 85, 1564-1571.
Oka, T., Oka, K. Scammell, T.E., Lee, C., Kelly, J.F., Nantel, F., Elmquist, J.K., & Saper, C.B. (2000). Relationship of EP1-4 Prostaglandin Recpetors With Rat Hypothalamic Cell Groups Involved in Lipopolysaccharide Fever Responses. The Journal of Comparative Neurology, 428, 20-32.
Roth, J., McClellan, J.L., Kluger, M.J., & Zeisberger, E. (1994). Attenuation of fever and release of cytokines after repeated injections of lipopolysaccharide in guinea-pigs. Journal of Phsyiology, 477 (1), 177-185
Tomazetti, J., Silva Avila, D., Ferreira, A.P.O., Martins, J.S., Souza, F.R., Royer, C., Rubin,
M.A., Oliveira, M.R., Bonacorso, H.G., Martins, M.A.P., Zanatta, N., & Mello, C.F. (2005). Baker yeast-induced fever in young rats: Characterization and validation of an animal model for antipyretics screening. Journal of Neuroscience Methods, 147(1), 29-35.
Walsh, R.N., & Cummins, R.A. (1976). The open field test: A critical review. Psychological Bulletin, 83(3), 482-504
Williams, G. C., & Nesse, R. (1991). The Dawn of Darwinian Medicine. The Quarterly Review of Biology, 66(1), 1-22.
Zhang, Y.H., Lu, J., Elmquist, J.K., & Saper, C.B. (2003). Specific Roles of Cyclooxygenase-1 and Cyclooxygenase-2 in Lipopolysaccharide-Induced Fever and Fos Expression
in Rat Brain. The Journal of Comparative Neurology, 463, 3-12.