Excitotoxic lesions of the rat medial prefrontal cortex. Effects on abnormal behaviors associated with neonatal hippocampal damage.
Neonatal excitotoxic damage of the ventral hippocampus (VH) is a heuristic model of schizophrenia. We investigated whether: (1) neonatal damage of the medial prefrontal cortex (mPFC) has effects similar to the neonatal VH lesion; and (2) intrinsic mPFC neurons contribute to the abnormal behaviors associated with VH lesions. Neonatal rats were lesioned in the mPFC. In adulthood, they showed attenuated locomotion in response to novelty, amphetamine, and MK-801, and enhanced apomorphine-induced stereotypies as compared to controls. Striatal D1 and D2 receptor mRNAs were unaltered. Another group was lesioned in the VH and additionally in the mPFC in adulthood. Destroying mPFC neurons normalized hyperlocomotion to novelty and amphetamine of the neonatally VH lesioned rats. Thus, neonatal damage of the mPFC does not provide a heuristic model of schizophrenia-like phenomena, in contrast to analogous damage of the VH. However, mPFC intrinsic neurons that have developed in the context of abnormal hippocampal connectivity may be responsible for abnormal behaviors in the neonatally VH lesioned rats.
Lipska
B K
BK
Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, St. Elizabeth's, Washington, DC 20032, USA.
al-Amin
H A
HA
Weinberger
D R
DR
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D012333:RNA, Messenger; D016291:Dizocilpine Maleate; D000661:Amphetamine; D001058:Apomorphine