Persistent neonatal Borna disease virus (BDV) infection of the brain causes chronic emotional abnormalities in adult rats.
Neonatal Borna disease virus (BDV) brain infection results in selective developmental damage to the hippocampal dentate gyrus and the cerebellum. When mature, neonatally BDV-infected rats show extreme locomotor hyperactivity and reduced freezing behavior in novel environments. Traditional interpretation of both of these behavioral abnormalities would suggest decreased anxiety in infected rats compared to normal animals. However, it also possible that the locomotor hyperactivity in infected rats reflects higher rather than reduced anxiety, and is the result of increased escape responses to aversive stimuli. The present experiments were undertaken to test a hypothesis about elevated anxiety in neonatally BDV-infected adult Lewis rats by studying their species-specific fear-related responses. Compared to normal subjects, BDV-infected rats exhibited locomotor hyperactivity and elevated defecation in a highly aversive, brightly lit open field. As expected, in a less aversive, dimly lit open field, uninfected controls increased ambulation, whereas infected rats significantly decreased locomotor activity and defecation. Unlike uninfected rats, BDV-infected rats exhibited an attenuated freezing response immediately after loud auditory stimuli. On the contrary, immediate freezing responses following footshock were comparable in the two groups of animals indicating an intact ability to freeze in BDV-infected rats. Despite a decreased baseline startle responsiveness, BDV-infected rats demonstrated increased sensitization of the startle response by preceding footshocks, suggesting a tendency toward elevated escape responses. Compared to normal subjects, BDV-infected rats showed decreased conditional freezing and elevated conditional defecation response in the context previously paired with aversive stimulation indicating sparing of an autonomic component of fear conditioning. The findings indicate that neonatally BDV-infected adult rats are hyperreactive to aversive stimuli, possibly as a result of chronic emotional abnormalities.
Pletnikov
M V
MV
Laboratory of Pediatric and Respiratory Viral Diseases, CBER, FDA, Bethesda, MD 20892, USA. pletnikov@cber.fda.gov
Rubin
S A
SA
Schwartz
G J
GJ
Moran
T H
TH
Sobotka
T J
TJ
Carbone
K M
KM
D000342:Affective Symptoms / Q000209:etiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000503:physiopathology; D001890:Borna Disease / Q000150:complications* / Q000473:pathology; D002494:Central Nervous System Infections / Q000150:complications* / Q000473:pathology; D002531:Cerebellum; D002908:Chronic Disease; D003214:Conditioning, Classical / Q000502:physiology; D005239:Fear / Q000502:physiology; D006624:Hippocampus; D006948:Hyperkinesis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013694:Temperament / Q000502:physiology