Affective / Emotional Behavior Assays

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Elevated Plus Maze

Standard test of anxiety in which the animal is placed in the center of an elevated, 4-arm maze where only two of the arms are enclosed. Anxiety-related behavior is measured as preference for the closed arms. Controls include total arm entries, which is generally considered to indicate non-specific locomotor activity (50-52).

Porsolt Forced Swim Test

This is a test of behavioral “despair” used to asses depression-like states. Essentially, a rodent is put in a tank of water from which there is no escape. The typical pattern of behavior is that the animals struggle and/or swim for some period of time. Eventually the animals “give up” and float. The latency to floating and the total time of floating are the typical measured parameters. While this may seem, at first glance, anthropomorphic the test has been extensively validated. Firstly, it is sensitive to and predictive of the success of anti-depressants. Secondly, many of the circumstances thought to promote depression in humans (unpredictable chronic stress, maternal and/or social isolation, inflammation) also induce behavioral “despair” in rodents. Lastly, the physiological responses, the brain regions and underlying mechanisms regulating behavior is this test has similarity to those found in humans, and to other assays of depression (53-56).

Social Preference

Deficits in social interaction are important manifestations of many developmental syndromes, sickness behavior and mood disorders. To quantify sociability, each rodent is scored on measures of exploration of two chambers – one containing a novel object and the other a novel conspecific. Normal rodents generally demonstrate a high degree of preference for exploring the conspecific animal.
The use of juvenile animals or ovariectomized adult female animals as social stimuli minimizes aggressive and sexual interactions.
This assay can also be modified to test olfactory memory, which is useful in the case of animals with visual deficits. After a suitable delay, the target animal is reintroduced to the arena, which now contains the familiar stimulus animal and a novel stimulus animal. Rats and mice generally spend significantly more time exploring the novel stimulus animal (57-59).
We can also perform a full ethological analysis of social interactions (59, 60).

Anhedonia

Lack of response to reward or pleasure (anhedonia) is a major symptom of depression. In rodents, this can be assessed by a decreased motivation to imbibe a palatable (sucrose) solution. Animals are exposed to sucrose solution 2 days-2 weeks before the test to establish baseline preference levels and to habituate them the novel flavor. To test sucrose preference, animals that were water-deprived for 12-18 h are presented with 1% sucrose solution or tap water for a period of 1 h. Sucrose preference is measured with reference to total intake. Anhedonia is defined as a reduction in sucrose preference relative to baseline levels or relative to control subjects (61).

Novelty Suppressed Feeding

Novelty-suppressed feeding (NSF) measures a rodent’s aversion to eating in a novel environment. This test assesses the latency of an animal to approach and eat a familiar food in an aversive environment. The test is sensitive to acute administration of anxiolytics and chronic antidepressant treatment but insensitive to acute antidepressants. Novelty suppressed feeding is therefore one of the few behavioral tests differentially sensitive to chronic versus acute effects of antidepressants (62).

Tail Suspension Test

This is used for assessment of depression when swimming in the Porsolt test is not recommended or possible (surgical implants, likelihood of hypothermia, subsequent use of water-based cognitive tasks, etc).  The mouse is suspended by the tail, and a total duration of immobility is recorded (63-65).

References

  1. Anseloni, VZ, Motta, V, Lima, G and Brandao, ML (1995). “Behavioral and pharmacological validation of the elevated plus maze constructed with transparent walls.” Braz J Med Biol Res 28(5): 597-601 [PMID: 8555981]
  2. Pellow, S, Chopin, P, File, SE and Briley, M (1985). “Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat.” J Neurosci Methods 14(3): 149-167 [PMID: 2864480]
  3. Doremus, TL, Varlinskaya, EI and Spear, LP (2006). “Factor analysis of elevated plus-maze behavior in adolescent and adult rats.” Pharmacol Biochem Behav 83(4): 570-577 [PMID: 16678892]
  4. Castagne, V, Moser, P, Roux, S and Porsolt, RD (2011). “Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice.” Curr Protoc Neurosci Chapter 8: Unit 8 10A [PMID: 21462162]
  5. Porsolt, RD, Deniel, M and Jalfre, M (1979). “Forced swimming in rats: hypothermia, immobility and the effects of imipramine.” Eur J Pharmacol 57(4): 431-436 [PMID: 258612]
  6. Porsolt, RD (1979). “Animal model of depression.” Biomedicine 30(3): 139-140 [PMID: 573643]
  7. Porsolt, RD, Anton, G, Blavet, N and Jalfre, M (1978). “Behavioural despair in rats: a new model sensitive to antidepressant treatments.” Eur J Pharmacol 47(4): 379-391 [PMID: 204499]
  8. Chang, YC, Cole, TB and Costa, LG (2017). “Behavioral Phenotyping for Autism Spectrum Disorders in Mice.” Curr Protoc Toxicol 72: 11 22 11-11 22 21 [PMID: 28463420] [PMC5494990].
  9. Yang, M, Abrams, DN, Zhang, JY, Weber, MD, Katz, AM, Clarke, AM, Silverman, JL and Crawley, JN (2012). “Low sociability in BTBR T+tf/J mice is independent of partner strain.” Physiol Behav 107(5): 649-662 [PMID: 22245067] [PMC3330157].
  10. Kaidanovich-Beilin, O, Lipina, T, Vukobradovic, I, Roder, J and Woodgett, JR (2011). “Assessment of social interaction behaviors.” J Vis Exp (48)[PMID: 21403628] [PMC3197404].
  11. Poshivalov, VP (1981). “Pharmaco-ethological analysis of social behaviour of isolated mice.” Pharmacol Biochem Behav 14 Suppl 1: 53-59 [PMID: 7243852]
  12. Papp, M, Willner, P and Muscat, R (1991). “An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress.” Psychopharmacology (Berl) 104(2): 255-259 [PMID: 1876670]
  13. Blasco-Serra, A, Gonzalez-Soler, EM, Cervera-Ferri, A, Teruel-Marti, V and Valverde-Navarro, AA (2017). “A standardization of the Novelty-Suppressed Feeding Test protocol in rats.” Neurosci Lett 658: 73-78 [PMID: 28803957]
  14. Steru, L, Chermat, R, Thierry, B and Simon, P (1985). “The tail suspension test: a new method for screening antidepressants in mice.” Psychopharmacology (Berl) 85(3): 367-370 [PMID: 3923523]
  15. Cryan, JF, Mombereau, C and Vassout, A (2005). “The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice.” Neurosci Biobehav Rev 29(4-5): 571-625 [PMID: 15890404]
  16. Can, A, Dao, DT, Terrillion, CE, Piantadosi, SC, Bhat, S and Gould, TD (2012). “The tail suspension test.” J Vis Exp (59): e3769 [PMID: 22315011] [PMC3353516].