Enhanced alpha1 adrenergic sensitivity in sensorimotor gating deficits in neonatal ventral hippocampus-lesioned rats.
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.
Kamath
Aarthi
A
Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, Quebec, Canada.
Al-Khairi
Irina
I
Bhardwaj
Sanjeev
S
Srivastava
Lalit K
LK
D000161:Acoustic Stimulation; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007051:Ibotenic Acid; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology*; D012565:Schizophrenic Psychology; D012677:Sensation / Q000235:genetics / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018690:Excitatory Amino Acid Agonists; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D007051:Ibotenic Acid; C014282:cirazoline; D011224:Prazosin