Enhanced alpha1 adrenergic sensitivity in sensorimotor gating deficits in neonatal ventral hippocampus-lesioned rats.

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 alpha1 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 alpha1 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 alpha1 adrenergic receptors. In order to test the functional relevance of alpha1 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 alpha1 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 alpha1 adrenergic receptor system that may mediate sensorimotor gating abnormalities reported in these animals.

• Authors: Aarthi Kamath, Irina Al-Khairi, Sanjeev Bhardwaj, Lalit K Srivastava
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 11 Issue 8 Pg. 1085-96 (Dec 2008) ISSN: 1461-1457 [Print] England
• PMID: 18460229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Excitatory Amino Acid Agonists
• Imidazoles
• Receptors, Adrenergic, alpha-1
• Ibotenic Acid
• cirazoline
• Prazosin

Topics

• Acoustic Stimulation
• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Animals, Newborn (physiology)
• Data Interpretation, Statistical
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Agonists
• Female
• Hippocampus (physiology)
• Ibotenic Acid
• Imidazoles (pharmacology)
• Male
• Prazosin (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, alpha-1 (genetics, physiology)
• Reflex, Startle (genetics, physiology)
• Schizophrenic Psychology
• Sensation (genetics, physiology)