The Female Urine Sniffing Test (FUST) of Reward-Seeking Behavior

  • Oz Malkesman
Part of the Neuromethods book series (NM, volume 63)


Abnormal reward-seeking behavior is a key feature in several psychiatric and neuroscience diseases. Though there are numerous paradigms for measuring reward-seeking behavior in rodents, each has limitations that affect the ability of the researcher to make conclusions on the reward-seeking behavior per se. Here, we describe a novel approach for monitoring reward-seeking behavior in rodents: the female urine-sniffing test (FUST). Lately, we found that sniffing of estrus female urine by male mice is a preferred activity of numerous mice strains and rats. In addition, this preferred activity was found to be accompanied by biological changes linked to hedonic and rewarding activities. The FUST was also been found to be sensitive to behavioral and genetic manipulation and to drug treatment related to depression and mania.

Key words

Hedonia Reward-seeking behavior Sniffing Estrus female urine 


  1. 1.
    American Psychiatric Association (2000): Diagnostic and Statistical Manual of Mental Disorders, Fourth edition. Washington, D.C: American Psychiatric Association.Google Scholar
  2. 2.
    Hasler G, Drevets WC, Gould TD, Gottesman, II, Manji HK (2006): Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry 60:93–105.PubMedCrossRefGoogle Scholar
  3. 3.
    Koob GF, Ahmed SH, Boutrel B, Chen SA, Kenny PJ, Markou A, O’Dell LE, Parsons LH, Sanna PP (2004). Neurobiological mechanisms in the transition from drug use to drug dependence. Neuroscience and Biobehavioral Reviews. 27:739–749.PubMedCrossRefGoogle Scholar
  4. 4.
    Barbano MF, Cador M (2007): Opioids for hedonic experience and dopamine to get ready for it. Psychopharmacology (Berl) 191:497–506.CrossRefGoogle Scholar
  5. 5.
    Klein DF (1974): Endogenomorphic depression. A conceptual and terminological revision. Arch Gen Psychiatry 31:447–454.PubMedCrossRefGoogle Scholar
  6. 6.
    Paredes RG (2009): Evaluating the neurobio­logy of sexual reward. Ilar J 50:15–27.PubMedGoogle Scholar
  7. 7.
    Crawley JN (2007): What’s Wrong With My Mouse: Behavioral Phenotyping of Transgenic and Knockout Mice. Wiley-Liss, New York.Google Scholar
  8. 8.
    Calcagnetti, D.J. & Schechter, M.D. (1992). Place conditioning reveals the rewarding aspect of social interaction in juvenile rats. Physiol. Behav. 51, 667–672.PubMedCrossRefGoogle Scholar
  9. 9.
    Tzschentke, T.M. (1999). The medial prefrontal cortex as a part of the brain reward system. Amino Acids. 19, 211–219.CrossRefGoogle Scholar
  10. 10.
    Willner P, Towell A, Sampson D, Sophokleous S, Muscat R. (1987). Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 93(3):358–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Pucilowski, O., Overstreet, D.H., Rezvani, A.H., Janowsky, D.S. (1993). Chronic Mild Stress-Induced Anedonia: Greater Effect in a Genetic Rat Model of Depression. Physiology & Behavior. 54, 1215–1220.CrossRefGoogle Scholar
  12. 12.
    Harris, R.B., Zhou, J., Youngblood, B.D., Smagin, G.N., & Ryan, D.H. (1998). Failure to change Exploration or Saccharin Preference In Rats Exposed to Chronic Mild Stress. Physiology & Behavior. 63(1), 91–100.CrossRefGoogle Scholar
  13. 13.
    Sclafani A (2006): Sucrose motivation in sweet “sensitive” (C57BL/6J) and “subsensitive” (129P3/J) mice measured by progressive ratio licking. Physiol Behav 87:734–744.PubMedCrossRefGoogle Scholar
  14. 14.
    Greenshaw, A. J. (1993). “Differential effects of ondansetron, haloperidol and clozapine on electrical self-stimulation of the ventral tegmental area.” Behav Pharmacol 4(5): 479–485.PubMedCrossRefGoogle Scholar
  15. 15.
    Sanchis-Segura C, Spanagel R (2006): Behavioural assessment of drug reinforcement and addictive features in rodents: an overview. Addict Biol 11:2–38.PubMedCrossRefGoogle Scholar
  16. 16.
    Malkesman O, Scattoni ML, Paredes D, Tragon T, Pearson B, Shaltiel G, Chen G, Crawley JN, Manji HK (2010): The Female Urine Sniffing Test: A Novel Approach for Assessing Reward-Seeking Behavior in Rodents. Biol Psyc 67:864–871.CrossRefGoogle Scholar
  17. 17.
    Martinez-Garcia F, Martinez-Ricos J, Agustin-Pavon C, Martinez-Hernandez J, Novejarque A, Lanuza E (2009): Refining the dual olfactory hypothesis: pheromone reward and odour experience. Behav Brain Res 200:277–286.PubMedCrossRefGoogle Scholar
  18. 18.
    Sipos ML, Kerchner M, Nyby JG (1992): An ephemeral sex pheromone in the urine of female house mice (Mus domesticus). Behav Neural Biol 58:138–143.PubMedCrossRefGoogle Scholar
  19. 19.
    Gregg B, Thiessen DD (1981): A simple method of olfactory discrimination of urines for the Mongolian gerbil, Meriones unguiculatus. Physiol Behav 26:1133–1136.PubMedCrossRefGoogle Scholar
  20. 20.
    Luo AH, Cannon EH, Wekesa KS, Lyman RF, Vandenbergh JG, Anholt RR (2002): Impaired olfactory behavior in mice deficient in the alpha subunit of G(o). Brain Res 941:62–71.PubMedCrossRefGoogle Scholar
  21. 21.
    Chadman KK, Gong S, Scattoni ML, Botluck SE, Gandhy SU, Heintz N, et al. (2008): Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Austism Res 1:147–158.CrossRefGoogle Scholar
  22. 22.
    Crawley JN, Chen T, Puri A, Washburn R, Sullivan TL, Hill JM, et al. (2007): Social approach behaviors in oxytocin knockout mice: comparison of two independent lines tested in different laboratory environments. Neuropeptides 41:145–163.PubMedCrossRefGoogle Scholar
  23. 23.
    Stack CM, Lim MA, Cuasay K, Stone MM, Seibert KM, Spivak-Pohis I, et al. (2008): Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice. Exp Neurol 211:67–84.PubMedCrossRefGoogle Scholar
  24. 24.
    Agmo A, Pfaff DW (1999): Research on the neurobiology of sexual behavior at the turn of the millennium. Behav Brain Res 105:1–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Hull EM, Dominguez JM (2006): Getting his act together: Roles of glutamate, nitric oxide, and dopamine in the medial preoptic area. Brain Research 1126:66–75.PubMedCrossRefGoogle Scholar
  26. 26.
    Cryan JF, Mombereau C (2004): In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9:326–357.PubMedCrossRefGoogle Scholar
  27. 27.
    Shaltiel G, Maeng S, Malkesman O, Pearson B, Schloesser RJ, Tragon T, et al. (2008): Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania. Mol Psychiatry 13:858–872.PubMedCrossRefGoogle Scholar
  28. 28.
    Rugh R (1990): The Mouse: Its Reproduction and Development. Oxford, UK: Oxford University Press.Google Scholar
  29. 29.
    Nyby J, Wysocki CJ, Whitney G, Dizinno G, Schneider J (1979): Elicitation of male mouse (Mus musculus) ultrasonic vocalizations: I. Urinary cues. J Comp Physiol Psychol 93: 957–975.CrossRefGoogle Scholar
  30. 30.
    Hoffman F, Musolf K, Penn DJ (2009): Freezing urine reduces its efficacy for eliciting ultrasonic vocalizations from male mice. Physiol Behav 96:602–605.CrossRefGoogle Scholar
  31. 31.
    Maeng S, Hunsberger JG, Pearson B, Yuan P, Wang Y, Wei Y, et al. (2008): BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments. Proc Natl Acad Sci USA 105:8766–8771.PubMedCrossRefGoogle Scholar
  32. 32.
    Gambarana C, Scheggi S, Tagliamonte A, Tolu P, De Montis MG (2001): Animal models for the study of antidepressant activity. Brain Res Brain Res Protoc 7:11–20.PubMedCrossRefGoogle Scholar
  33. 33.
    Henn FA, Edwards E, Muneyyirci J (1993): Animal models of depression. Clin Neurosci 1:152–156.Google Scholar
  34. 34.
    Strekalova T, Gorenkova N, Schunk E, Dolgov O, Bartsch D (2006): Selective effects of citalopram in a mouse model of stress-induced anhedonia with a control for chronic stress. Behav Pharmacol 17:271–287.PubMedCrossRefGoogle Scholar
  35. 35.
    Forbes NF, Stewart CA, Matthews K, Reid IC (1996): Chronic mild stress and sucrose consumption: validity as a model of depression. Physiol Behav 60:1481–1484.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Laboratory of Molecular Pathophysiology, Intramural Research ProgramNational Institute of Mental Health, National Institutes of HealthBethesdaUSA

Personalised recommendations