期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 11, 期 8, 页码 1085-1096出版社
OXFORD UNIV PRESS
DOI: 10.1017/S1461145708008845
关键词
Animal model; behaviour; norepinephrine; prepulse inhibition; schizophrenia
资金
- Canadian Institutes of Health Research
Neonatal ventral hippocampus (nVH) lesion in rats is a widely used animal model of schizophrenia due to the predominantly post-pubertal emergence of many schizophrenia-like behaviours. Our previous studies have shown increased ligand binding of alpha(1) adrenergic receptors (AR) in the frontal cortex of post-pubertal, but not pre-pubertal, nVH-lesioned rats, compared to sham-lesioned control rats. Moreover, pretreatment with the alpha(1) adrenergic receptor antagonist prazosin reversed amphetamine-induced hyperlocomotion in controls, but failed to do so in lesioned animals. This led to our hypothesis that nVH lesions may lead to post-pubertal hyperactivity of alpha(1) adrenergic receptors. In order to test the functional relevance of alpha(1) adrenergic hyperactivity to schizophrenia-like behaviours of nVH-lesioned animals, we conducted prepulse inhibition (PPI) studies in post-pubertal (postnatal days 56-120) sham and lesioned animals in response to systemic injections of alpha(1) adrenergic receptor antagonist and agonist, prazosin and cirazoline, respectively. Our results show that PPI deficits in nVH-lesioned animals were reversed with prazosin treatment, without a significant effect on PPI in sham animals. Further, at various doses, cirazoline had a significantly greater PPI disruptive effect in nVH-lesioned animals than in sham animals. Together, these results suggest that nVH-lesioned animals show a hyperactive alpha(1) adrenergic receptor system that may mediate sensorimotor gating abnormalities reported in these animals.
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