Behavioral effects of neonatal and adult excitotoxic lesions of the mediodorsal thalamus in the adult rat.
We examined in the rat, the effects of neonatal (postnatal Day 7) and adult excitotoxic lesions of the mediodorsal thalamus (MDT), a brain area innervating the prefrontal cortex and implicated as a site of neuropathology in schizophrenia. Previous studies showed that rats with neonatal excitotoxic damage of the ventral hippocampus (VH), used as an animal model of this disorder, display in young adulthood a variety of abnormalities reminiscent of schizophrenia, including hyperactivity to stressful stimuli and amphetamine. It has been speculated that behavioral abnormalities of the neonatally VH lesioned animals are mediated through MDT projections to the prefrontal cortex. We tested if rats with ibotenic acid (1.5 microg per hemisphere in neonates, 2 microg in adults) lesions of MDT exhibited motor hyperactivity in the same experimental conditions (i.e. in response to novelty, saline injections and amphetamine administration) as rats with the VH lesions. We found that, in contrast to rats with VH lesions, neonatally lesioned MDT rats showed reduced vertical activity in response to amphetamine and no changes in locomotor activity to novelty, saline or amphetamine injections 7 weeks postlesion. Adult lesioned MDT rats exhibited no changes in motor activity as compared to controls at 7 weeks postlesion. These results indicate that neonatal or adult excitotoxic lesions of MDT do not produce behavioral changes analogous to those seen after neonatal VH lesions and do not appear to reproduce animal model-like features of schizophrenia.
Lipska
Barbara K
BK
Intramural Research Program, Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 4N306, Bethesda, MD 20892-1385, USA. lipskab@intra.nimh.nih.gov
Luu
Suly
S
Halim
Nader D
ND
Weinberger
Daniel R
DR
D000375:Aging / Q000502:physiology* / Q000523:psychology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D005260:Female; D008297:Male; D009043:Motor Activity / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000503:physiopathology; D013788:Thalamus / Q000033:anatomy & histology / Q000502:physiology*
D004298:Dopamine