TY - JOUR
T1 - Rats selectively bred for low levels of play-induced 50kHz vocalizations as a model for Autism Spectrum Disorders
T2 - A role for NMDA receptors
AU - Burgdorf, Jeffrey
AU - Moskal, Joseph R.
AU - Brudzynski, Stefan M.
AU - Panksepp, Jaak
N1 - Funding Information:
This research was supported by grants from the Ralph and Marian Falk Medical Research Trust (Chicago, IL) to JRM, Hope for Depression Research Foundation to JSB, JRM, SMB, JP and NIMH R01-MH094835 to JSB. We would like to thank the Northwestern University Behavioral Phenotyping Core for it's assistance, and Ms Mary Schmidt for her expert technical assistance.
PY - 2013/8/15
Y1 - 2013/8/15
N2 - Early childhood autism is characterized by deficits in social approach and play behaviors, socio-emotional relatedness, and communication/speech abnormalities, as well as repetitive behaviors. These core neuropsychological features of autism can be modeled in laboratory rats, and the results may be useful for drug discovery and therapeutic development. We review data that show that rats selectively bred for low rates of play-related pro-social ultrasonic vocalizations (USVs) can be used to model social deficit symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes, and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR functional glycine site partial agonist, GLYX-13, rescued the deficits in play-induced pro-social 50-kHz USVs and reduced monotonous USVs. Since the NMDA receptor has been implicated in the genesis of autistic symptoms, it is possible that GLYX-13 may be of therapeutic value in the treatment of autism.
AB - Early childhood autism is characterized by deficits in social approach and play behaviors, socio-emotional relatedness, and communication/speech abnormalities, as well as repetitive behaviors. These core neuropsychological features of autism can be modeled in laboratory rats, and the results may be useful for drug discovery and therapeutic development. We review data that show that rats selectively bred for low rates of play-related pro-social ultrasonic vocalizations (USVs) can be used to model social deficit symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes, and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR functional glycine site partial agonist, GLYX-13, rescued the deficits in play-induced pro-social 50-kHz USVs and reduced monotonous USVs. Since the NMDA receptor has been implicated in the genesis of autistic symptoms, it is possible that GLYX-13 may be of therapeutic value in the treatment of autism.
KW - Autism
KW - GLYX-13
KW - NMDA Receptor
KW - Rat
KW - Selective breeding
KW - Ultrasonic vocalization
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U2 - 10.1016/j.bbr.2013.04.022
DO - 10.1016/j.bbr.2013.04.022
M3 - Article
C2 - 23623884
AN - SCOPUS:84880331581
SN - 0166-4328
VL - 251
SP - 18
EP - 24
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -