Altered social behavior in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice.
The olfactory bulb plays a critical role in odor discrimination and in processing olfactory cues controlling social behavior in mammals. Given that the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1) is highly expressed in the olfactory bulb, we examined its role in regulating olfaction and social investigation. We found that olfactory detection of nonsocial stimuli was similar in PAC1-deficient mice and wild-type (WT) littermates. In contrast, PAC1-deficient mice displayed markedly abnormal social behaviors. PAC1-deficient mice exhibited a faster decrease in social investigation after repeated exposure to social cues or ovariectomized female urine compared with WT mice. Moreover, PAC1-deficient females exhibited delayed affiliative behavior when housed with novel males, and PAC1-deficient males displayed excessive sexual mounting toward both females and males as well as reduced aggression and increased licking and grooming toward intruder males. In aggregate, these results uncover PAC1 signaling as an important factor in the development and/or functioning of neural pathways associated with pheromone processing and the regulation of social interactions in mice. In turn, these studies raise the potential clinical relevance of PACAP signaling dysfunctions in neuropsychiatric disorders characterized by social reciprocity impairments such as autism spectrum disorders.
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Arnaud
A
Nicot
Timothy
T
Otto
Philippe
P
Brabet
Emanuel M
EM
Dicicco-Bloom
D000374:Aggression; D000818:Animals; D001522:Behavior, Animal; D001973:Bromodeoxyuridine / Q000032:analysis; D005260:Female; D006185:Habituation, Psychophysiologic; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009812:Odorants; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D012726:Sexual Behavior, Animal; D012903:Smell; D012919:Social Behavior; D014556:Urine
C495503:ADCYAP1R1 protein, human; C495504:Adcyap1r1 protein, mouse; D011956:Receptors, Cell Surface; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D001973:Bromodeoxyuridine