Enhanced α 1 adrenergic sensitivity in sensorimotor gating deficits in neonatal ventral hippocampus-lesioned rats

Aarthi Kamath, Irina Al khairi, Sanjeev Bhardwaj, Lalit K. Srivastava

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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 α 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 α 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 α 1 adrenergic receptors. In order to test the functional relevance of α 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 α 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 α 1 adrenergic receptor system that may mediate sensorimotor gating abnormalities reported in these animals.

Original languageEnglish
Pages (from-to)1085-1096
Number of pages12
JournalInternational Journal of Neuropsychopharmacology
Volume11
Issue number8
DOIs
Publication statusPublished - 1 Dec 2008

Keywords

  • Animal model
  • Behaviour
  • Norepinephrine
  • Prepulse inhibition
  • Schizophrenia

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