Effects of behavioral and neurochemical changes on adult excitotoxic lesion of the ventral hippocampus.
BACKGROUND
The postmortem and magnetic resonance imaging studies for schizophrenic patients showed neuropathological abnormalities including neuron loss and volume reduction in ventral hippocampus (VH), some longitudinal studies suggest these changes may be a neurodegenerative process.


OBJECTIVE
The present study examined the effects of adult bilateral VH lesions on a dopaminergic stimulant, methamphetamine (METH)-induced and an N-methyl-(D)-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801)-induced behavioral and neurochemical changes in rats, in order to evaluate a potential of adult VH lesion animals for a model of schizophrenia.


METHODS
To study the behavioral effects after bilateral VH lesions in adult rats, locomotor activity was measured individually by an infra-red sensor. Extracellular concentrations of dopamine in the nucleus accumbens (NAc) were measured using in vivo brain microdialysis.


RESULTS
The bilateral adult VH lesion rats showed a significant enhanced hyperlocomotion in response to METH but no changes to MK-801 and phencyclidine; while bilateral adult VH lesion enhanced METH-induced increasing dopamine levels in the NAc.


CONCLUSIONS
The bilateral adult VH lesions enhanced locomotor activity, which related to increased dopamine releases in the NAc, induced by a dopaminergic stimulant; these findings may suggest a potential of adult VH lesion animal for a model reflecting dopamine D2 receptor antagonist-responsive pathophysiology of schizophrenia by way of neurodegenerative processes.
Fang
Yi Ru
YR
Shanghai Mental Health Center, Department of Psychiatry, School of Medicine, Shanghai JiaoTong University, 600 South Wan Ping Road, Shanghai 200030, China. fang-yr@online.sh.cn
Abekawa
Tomohiro
T
Ito
Koki
K
Li
Xiao Bai
XB
Koyama
Tsukasa
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000009:adverse effects; D004298:Dopamine / Q000032:analysis; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced; D009498:Neurotoxins / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced*
D009498:Neurotoxins; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D004298:Dopamine