Rodent Models of Depression: Learned Helplessness Using a Triadic Design in Rats

Robert C. Durgam1

1 University of New Hampshire, Durgam, New Hampshire
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 8.10B
DOI:  10.1002/0471142301.ns0810bs14
Online Posting Date:  May, 2001
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Certain types of human depression are precipitated by stressful life events, and vulnerable individuals experiencing these stressors may develop clinical depression. Understanding the neurobiology of stress vulnerability (depression) as well as stress resiliency (coping) is critical for guiding the development of novel pharmacotherapeutic agents for stress‐related disorders such as depression in humans. The use of a triadic design (escapable shock, yoked‐inescapable shock and restrained control) allows the investigator to examine the various sequella of stress exposure, while manipulating and quantifying the impact of psychological dynamics of stress such as active behavioral coping (i.e., stress control). Both escape and yoked subjects are exposed to the identical amount, intensity, pattern and duration of stress. The critical distinction between these two groups is that the escape group has the opportunity to terminate the shock stress by turning a wheel at the front of a chamber, while wheel‐turning for the yoked subject is of no consequence. Any difference observed between the escape and yoked subjects is a result of the effects of coping, rather than stress exposure per se. The restrained group is included to control for the effects of handling. Any differences between this group and the escape and yoked subjects reflects the impact of stress per se.

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Table of Contents

  • Basic Protocol 1: A Triadic Design to Produce Behavioral Learned Helplessness in Rats
  • Support Protocol 1: Construction of Wheel‐Turn Boxes
  • Commentary
  • Figures
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Basic Protocol 1: A Triadic Design to Produce Behavioral Learned Helplessness in Rats

  • 180‐ to 200‐g male Sprague‐Dawley rats (e.g., Charles River Laboratories)
  • Standard rat chow
  • Electrode paste (Redux Paste, Hewlett‐Packard)
  • Transparent polyethylene tub cages, 53.8 × 30 × 20 cm (21 ½ × 12 × 8 in., length × width × height), with wire tops (e.g., Lab Products)
  • 7.5‐W house lights
  • Sound‐attenuating chambers (constructed in house of wood and particle board), outside 108.8 × 55 × 52.5 cm (43 ½2 × 22 × 21 in.), inside 93.8 × 41.2 × 37.5 cm (37 ½2 × 16 ½× 15 in., L × W × H), equipped with an exhaust fan and a 30 × 16.2–cm (12 × 6 ½ –in., L × H) window in the front door
  • Wheel‐turn boxes (see protocol 2)
  • Cloth athletic adhesive tape (several rolls; e.g., Johnson and Johnson)
  • Brass plate electrodes attached to wire snap leads (from standard electromechanical relay connectors)
  • Opaque partition to fit lengthwise in sound‐attenuating chamber
  • Personal computer (e.g., IBM‐AT)
  • Computer software: Turbo Pascal or similar in‐house control programs to control tail shock presentations and record latencies, and data analysis software (e.g., SPSS)
  • Shock source: direct current (DC) generator (e.g., Lafayette Instrument model no. 82400)
  • Two‐chambered shuttle boxes (BRS/LVE) equipped with a sonalert noise generator in the middle of the top and a tray of wood shavings
  • Shock generator‐scrambler (BRS/LVE) to produce grid shock to the shuttle‐box floor
NOTE: The stress controllability pretreatment (day 1) should be performed during the first 6 hr of the light cycle to avoid circadian fluctuations of steroid hormones (e.g., corticosterone) that may influence stress reactivity and thereby add variability to the data.

Support Protocol 1: Construction of Wheel‐Turn Boxes

  • 0.6‐cm (¼‐in.) thick Plexiglas
  • Epoxy adhesive
  • Two 1‐in2 brass hinges (available in hardware stores)
  • Tube made of 0.6‐cm (¼‐in.) thick Plexiglas, 7.6 cm (3 in.) outer diameter, 5.7 cm (2 ¼ in.) long
  • Two 9.5‐cm (3 ¾‐in.) diameter circles of 0.6‐cm (¼‐in.) thick Plexiglas
  • Twelve 0.6 × 7.0‐cm (¼ × 2 3 ¾‐in., diameter × length) aluminum bars
  • Two 7.5 × 9.0‐cm (3 × 3 ½ ‐in., length × height) pieces of 0.6‐cm (¼ ‐in.) thick Plexiglas
  • 0.6 × 16.5‐cm (¼ × 6 ½ ‐in., diameter × length) metal rod
  • 2.5 × 2.5‐cm (1 × 1‐in.) square piece of 0.6‐cm (¼ ‐in.) thick Plexiglas
  • Microswitches (model L96, Micro, available from Digi‐Key) to count wheel revolutions
  • Torque wrench
  • 1.9 × 1.9 × 17.1‐cm (¾×¾× 6 ¾‐in.) Plexiglas rod
  • 0.2‐cm thick (1/16 ‐in. thick), 1.3 × 1.3‐cm (½ × ½‐in.) square brass plates attached to wires with snap leads
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Literature Cited

Literature Cited
   Church, R.M. 1964. Systematic effect of random error in the yoked control design. Psychol. Bull. 64:122‐131.
   Drugan, R.C., Ader, D.N., and Maier, S.F. 1985. Shock controllability and the nature of stress‐induced analgesia. Behav. Neurosci. 99:791‐801.
   Drugan, R.C., Crawley, J.N., Paul, S.M., and Skolnick, P. 1987. Buspirone attenuates learned helplessness behavior in rats. Drug Dev. Res. 10:63‐67.
  Drugan, R.C., Basile, A.S., Ha, J.H., Healy, D.J., and Ferland, R.J. 1997. Analysis of the importance of controllable versus uncontrollable stress on subsequent behavioral and physiological functioning. Brain Res. Protoc. 2:69‐74.
   Henn, F.A., Edwards, E., and Muneyyirci, J. 1993. Animal models of depression. Clin. Neurosci. 1:152‐156.
   Jackson, R.L., Maier, S.F., and Rapaport, P.M. 1978. Exposure to inescapable shock produces both activity and associative deficits in the rat. Learn. Motiv. 9:69‐98.
   Maier, S.F. and Seligman, M.E.P. 1976. Learned helplessness: Theory and evidence. J. Exp. Psychol. Gen. 105:3‐46.
   Maier, S.F., Albin, R.W., and Testa, T.J. 1973. Failure to learn to escape in rats previously exposed to inescapable shock depends on the nature of the escape response. J. Comp. Physiol. Psychol. 85:581‐592.
   Maier, S.F., Drugan, R.C., and Grau, J.W. 1982. Controllability, coping behavior and stress‐induced analgesia in the rat. Pain 12:47‐56.
   Overmier, J.B. and Seligman, M.E.P. 1967. Effects of inescapable shock upon subsequent escape and avoidance learning. J. Comp. Physiol. Psychol. 63:28‐33.
   Seligman, M.E.P. and Maier, S.F. 1967. Failure to escape traumatic shock. J. Exp. Psychol. 74:1‐9.
   Wasserman, E.A. 1988. Response bias in the yoked control procedure. Behav. Brain Sci. 11:477‐478.
   Weiss, J.M., Stone, E.A., and Harrell, N. 1970. Coping behavior and brain norepinephrine in rats. J. Comp. Physiol. Psychol. 72:153‐160.
   Weiss, J.M., Goodman, P.A., Losito, B.G., Corrigan, S., Charry, J.M., and Bailey, W.H. 1981. Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, sopamine and serotonin levels in various regions of the rat brain. Brain Res. Rev. 3:167‐205.
   Wieland, S., Boren, J.L., Consroe, P.F., and Martin, A. 1986. Stock differences in the susceptibility of rats to learned helplessness training. Life Sci. 39:937‐944.
Key References
   Maier and Seligman, 1976. See above.
  Provides a perspective on the theory and early use of the triadic design.
   Maier, S.F. and Warren, D.A. 1988. Controllability and safety signals exert dissimilar proactive effects on nociception and escape performance. J. Exp. Psychol. Anim. Behav. Process. 14:18‐25.
  Provocative data demonstrating that the effects of controllability in the triadic design are distinct from what one might envision from a safety signal hypothesis.
   Mineka, S. and Henderson, R.W. 1985. Controllability and predictability in acquired motivation. Annu. Rev. Psychol. 36:495‐529.
  This article offers important insights and a review of the data on whether controllability and predictability are co‐mingled in the standard triadic design.
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