The female urine sniffing test: a novel approach for assessing reward-seeking behavior in rodents.
BACKGROUND
Abnormal hedonic behavior is a key feature of many psychiatric disorders. Several paradigms measure reward-seeking behavior in rodents, but each has limitations. We describe a novel approach for monitoring reward-seeking behavior in rodents: sniffing of estrus female urine by male mice, along with number of ultrasonic vocalizations (USVs) emitted during the test.


METHODS
The female urine sniffing test (FUST) was designed to monitor reward-seeking activity in rodents together with tests of helplessness and sweet solution preference. USVs and dopamine release from the nucleus accumbens (NAc) were recorded. Sniffing activity was measured in 1) manipulation-naive C57BL/6J and 129S1/SVImJ mice and Wistar-Kyoto rats; 2) stressed mice; 3) two groups of mice that underwent the learned helplessness paradigm-one untreated, and one treated with the SSRI citalopram; and 4) GluR6 knockout mice, known to display lithium-responsive, mania-related behaviors.


RESULTS
Males from all three strains spent significantly longer sniffing female urine than sniffing water. Males emitted USVs and showed significantly elevated NAc dopamine levels while sniffing urine. Foot-shock stress significantly reduced female urine sniffing time. Compared with mice that did not undergo the LH paradigm, LH males spent less time sniffing female urine, and citalopram treatment alleviated this reduction. Compared with their wildtype littermates, GluR6KO males sniffed female urine longer and showed enhanced saccharin preference.


CONCLUSIONS
In rodents, sniffing female urine is a preferred activity accompanied by biological changes previously linked to reward-seeking activities. The FUST is sensitive to behavioral and genetic manipulation and to relevant drug treatment.
Malkesman
Oz
O
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA.
Scattoni
Maria Luisa
ML
Paredes
Daniel
D
Tragon
Tyson
T
Pearson
Brandon
B
Shaltiel
Galit
G
Chen
Guang
G
Crawley
Jacqueline N
JN
Manji
Husseini K
HK
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal; D015283:Citalopram / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004597:Electroshock / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D008094:Lithium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D018092:Kainic Acid Receptors / Q000172:deficiency; D012201:Reward; D012439:Saccharin / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012903:Smell / Q000502:physiology*; D013045:Species Specificity; D013549:Sweetening Agents / Q000494:pharmacology; D014465:Ultrasonics; D014556:Urine; D014828:Vocalization, Animal; D000097806:GluK2 Kainate Receptor
D014150:Antipsychotic Agents; D015283:Citalopram; D004298:Dopamine; D008094:Lithium; D018092:Kainic Acid Receptors; D012439:Saccharin; D017367:Selective Serotonin Reuptake Inhibitors; D013549:Sweetening Agents; D000097806:GluK2 Kainate Receptor