Neonatal intrahippocampal immune challenge alters dopamine modulation of prefrontal cortical interneurons in adult rats.
BACKGROUND
Among the diverse animal models proposed for schizophrenia, the neonatal ventral hippocampal lesion (NVHL) is one of the most widely used. However, its construct validity can be questioned because there is no evidence of a lesion present in schizophrenia. Other approaches that have tried to capture environmental influences on development include diverse models of maternal infection.


METHODS
As the early postnatal days in rodents are equivalent to the third trimester of human pregnancy in terms of brain development, we decided to test whether a neonatal immune challenge with an injection of the bacterial endotoxin lipopolysaccharide (LPS) into the ventral hippocampus caused deficits in interneuron function similar to those reported for the NVHL.


RESULTS
Neonatal LPS injection caused a persistent elevation in cytokines in several brain regions, deficits in prepulse inhibition of the acoustic startle response, and a loss of the periadolescent maturation in the response of prefrontal cortical fast-spiking interneurons to dopamine.


CONCLUSIONS
The same phenotypes elicited by a NVHL can be obtained with an intrahippocampal immune challenge, suggesting that perinatal environmental factors can affect adult prefrontal interneuron maturation during adolescence.
Feleder
Carlos
C
Department of Pharmaceutical Sciences, Albany College of Pharmacy, New York, USA.
Tseng
Kuei Yuan
KY
Calhoon
Gwendolyn G
GG
O'Donnell
Patricio
P
D000161:Acoustic Stimulation / Q000009:adverse effects; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology*; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D018491:Dopamine Agonists; D008070:Lipopolysaccharides; D019257:Quinpirole; D004298:Dopamine