Developmental brain injury associated with abnormal play behavior in neonatally Borna disease virus-infected Lewis rats: a model of autism.
Play behavior, nonsocial exploratory activity, and nonplay social interaction were observed in male juvenile Lewis rats with brain developmental injury following neonatal infection with Borna disease virus (BDV). These behaviors were tested using the 'intruder-resident' paradigm, with social isolation of residents for six days prior to testing. Four experimental pairings of infected (BDV) and uninfected (NL) rats were studied as follows: NL-NL; NL BDV; BDV NL; and BDV-BDV (the first member is the resident, the second member is the intruder). Observation of social activities was carried out for 10 min on two consecutive days. Nonsocial exploratory activity (e.g. ambulation and rearing) was similar in BDV and NL residents. Duration of nonplay social investigation (e.g. sniffing, approach, and follow) was higher in BDV residents as compared to NL residents when tested on the first test day. On the second day, all rats showed similar level of nonplay social interaction. When confronted with NL intruders, NL residents exhibited significantly more play behavior compared to the NL-BDV, BDV NL and BDV-BDV pairs, when play behavior was measured by the number of 'pins'. Moreover, irrespective of a type of intruder, NL residents demonstrated higher play soliciting behavior than BDV residents, indicating attenuated readiness to play in BDV-infected rats. The number of pins and play solicitations in BDV-NL pairs significantly increased over the two days of testing, while play activity in NL-BDV pairs declined on the second test day. This pattern suggests that the degree of social reinforcement on the first day of testing affected the level of play on the second day. These data demonstrate deficits in play behavior and other social interactions following BDV-associated developmental brain injury, thus supporting the value of the neonatally BDV-infected rat as an animal model of autism.
Pletnikov
M V
MV
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. pletnikov@a1.cber.fda.gov
Rubin
S A
SA
Vasudevan
K
K
Moran
T H
TH
Carbone
K M
KM
D000818:Animals; D000831:Animals, Newborn; D001321:Autistic Disorder / Q000503:physiopathology*; D001890:Borna Disease / Q000503:physiopathology*; D001891:Borna disease virus / Q000472:pathogenicity; D001921:Brain / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D008297:Male; D010988:Play and Playthings; D011247:Pregnancy; D051381:Rats; D011917:Rats, Inbred Lew; D012056:Reinforcement, Social; D012919:Social Behavior; D014774:Virulence