TY - JOUR
T1 -
Enhanced α
1
adrenergic sensitivity in sensorimotor gating deficits in neonatal ventral hippocampus-lesioned rats
AU - Kamath, Aarthi
AU - Al khairi, Irina
AU - Bhardwaj, Sanjeev
AU - Srivastava, Lalit K.
PY - 2008/12/1
Y1 - 2008/12/1
N2 -
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.
AB -
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.
KW - Animal model
KW - Behaviour
KW - Norepinephrine
KW - Prepulse inhibition
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=55549106165&partnerID=8YFLogxK
U2 - 10.1017/S1461145708008845
DO - 10.1017/S1461145708008845
M3 - Article
C2 - 18460229
AN - SCOPUS:55549106165
VL - 11
SP - 1085
EP - 1096
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
SN - 1461-1457
IS - 8
ER -