PMID- 23637901
OWN - NLM
STAT- MEDLINE
DCOM- 20131209
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 4
DP  - 2013
TI  - Pyrazine analogues are active components of wolf urine that induce avoidance and 
      freezing behaviours in mice.
PG  - e61753
LID - 10.1371/journal.pone.0061753 [doi]
LID - e61753
AB  - BACKGROUND: The common grey wolf (Canis lupus) is found throughout the entire 
      Northern hemisphere and preys on many kinds of mammals. The urine of the wolf 
      contains a number of volatile constituents that can potentially be used for 
      predator-prey chemosignalling. Although wolf urine is put to practical use to 
      keep rabbits, rodents, deer and so on at bay, we are unaware of any prior 
      behavioural studies or chemical analyses regarding the fear-inducing impact of 
      wolf urine on laboratory mice. METHODOLOGY/PRINCIPAL FINDINGS: Three wolf urine 
      samples harvested at different times were used in this study. All of them induced 
      stereotypical fear-associated behaviors (i.e., avoidance and freezing) in female 
      mice. The levels of certain urinary volatiles varied widely among the samples. To 
      identify the volatiles that provoked avoidance and freezing, behavioural, 
      chemical, and immunohistochemical analyses were performed. One of the urine 
      samples (sample C) had higher levels of 2,6-dimethylpyrazine (DMP), 
      trimethylpyrazine (TMP), and 3-ethyl-2,5-dimethyl pyrazine (EDMP) compared with 
      the other two urine samples (samples A and B). In addition, sample C induced 
      avoidance and freezing behaviours more effectively than samples A and B. 
      Moreover, only sample C led to pronounced expression of Fos-immunoreactive cells 
      in the accessory olfactory bulb (AOB) of female mice. Freezing behaviour and Fos 
      immunoreactivity were markedly enhanced when the mice were confronted with a 
      mixture of purified DMP, TMP, and EDMP vs. any one pyrazine alone. 
      CONCLUSIONS/SIGNIFICANCE: The current results suggest that wolf urinary volatiles 
      can engender aversive and fear-related responses in mice. Pyrazine analogues were 
      identified as the predominant active components among these volatiles to induce 
      avoidance and freezing behaviours via stimulation of the murine AOB.
FAU - Osada, Kazumi
AU  - Osada K
AD  - Division of Physiology, Department of Oral Biology, School of Dentistry, Health 
      Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan. 
      Erin.Gillam@ndsu.edu
FAU - Kurihara, Kenzo
AU  - Kurihara K
FAU - Izumi, Hiroshi
AU  - Izumi H
FAU - Kashiwayanagi, Makoto
AU  - Kashiwayanagi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130424
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Pyrazines)
SB  - IM
MH  - Animals
MH  - *Avoidance Learning
MH  - *Behavior, Animal
MH  - Mice
MH  - Odorants
MH  - Olfactory Bulb/drug effects/metabolism
MH  - *Panic
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - *Pyrazines/chemistry/pharmacology/urine
MH  - *Wolves/urine
PMC - PMC3634846
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/03 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/04/24
CRDT- 2013/05/03 06:00
PHST- 2012/12/10 00:00 [received]
PHST- 2013/03/13 00:00 [accepted]
PHST- 2013/05/03 06:00 [entrez]
PHST- 2013/05/03 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/04/24 00:00 [pmc-release]
AID - PONE-D-12-38821 [pii]
AID - 10.1371/journal.pone.0061753 [doi]
PST - epublish
SO  - PLoS One. 2013 Apr 24;8(4):e61753. doi: 10.1371/journal.pone.0061753. Print 2013.