Reduction of Prepulse Inhibition (PPI) after neonatal excitotoxic lesion of the ventral thalamus in pubertal and adult rats.
BACKGROUND
Growing evidence indicates the role of the thalamus in schizophrenia. The ventral part of the thalamus has been investigated in a few post-mortem studies, suggesting a possible neurodevelopmental etiology of the reduced neuron number.


METHODS
Here we adapt a neurodevelopmental animal model, the neonatal excitotoxic brain lesion, to the ventral thalamus (VT) of Sprague-Dawley rats. At postnatal day (PD) 7 male pups were bilaterally infused into the VT using ibotenic acid (IBA) or artificial cerebrospinal fluid. Repeated measurements of prepulse inhibition (PPI) of the acoustic startle response, reviewed as a measure of sensorimotor gating deficits in neuropsychiatric disorders such as schizophrenia, were performed during puberty and adulthood.


RESULTS
IBA animals showed lower PPI (p<0.001) compared to controls. The extent of VT lesions correlated negatively with PPI levels (p<0.001). PPI deficits in IBA animals were observed at PD 43 and PPI levels increased significantly after puberty without reaching control levels. Acute or subchronic clozapine treatment did not significantly restore low PPI in IBA rats.


CONCLUSIONS
The present data suggest that the VT may be involved in the PPI deficits observed in schizophrenia.
Department of Psychiatry, Ruhr University Bochum, Bochum, Germany. Rainer.Wolf@ruhr-uni-bochum.de
R
R
Wolf
K
K
Matzke
K
K
Paelchen
H
H
Dobrowolny
B
B
Bogerts
H
H
Schwegler
D000367:Age Factors; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology*
D014150:Antipsychotic Agents; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D003024:Clozapine