Spontaneously Hypertensive Rats (SHR) present deficits in prepulse inhibition of startle specifically reverted by clozapine

Abstract

Deficits in an operational measure of sensorimotor gating - the prepulse inhibition of startle (PPI) - are presented in psychiatric disorders such as schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). Some previous studies showed that the spontaneously hypertensive rats (SHR) present PPI deficit. Although SHR is suggested as an animal model to study ADHD, we have suggested that the behavioral phenotype of this strain mimics some aspects of schizophrenia. The aim of this study was to characterize the PPI response in SHR. Pharmacological characterization consisted in the evaluation of the effects of the following drugs administered to adult Wistar rats (WR) and SHR previously to the PPI test: amphetamine (used for ADHD and also a psychotomimetic drug), haloperidol and clozapine (antipsychotic drugs), metoclopramide (dopamine antagonist without antipsychotic properties) and carbamazepine (mood stabilizer). Our results showed that SHR presented reduced PPI. This deficit was similar to that induced by amphetamine in WR. Only the atypical antipsychotic clozapine improved the PPI deficit observed in SHR. These findings reinforce the SHR strain as an animal model to study several aspects of schizophrenia, including the abnormalities in sensorimotor gating associated with this disease.

Common prefrontal cortical gene expression profiles between adolescent SHR/NCrl and WKY/NCrl rats which showed inattention behavior

“…It has also been shown that NR3A knockout mice displayed increased prepulse inhibition [40], a measure of sensorimotor gating, which is a neurological process that occurs within the context of attentional processes. In a recent study, SHRs were also reported to present abnormalities in prepulse inhibition [41]. Whether changes in Grin3a brain gene expression in the SHR correlate with sensorimotor gating deficits or specifically, inattention in this rat strain should be clarified in future studies.…”

Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine

“…This was recently confirmed in spontaneously hypertensive rats (SHRs). These animals exhibit behavioral changes such as a basal disruption in PPI that have been associated with schizophrenia, since they are reversed by clozapine (Levin et al 2011). Similar to antipsychotic drugs, CBD also increases the PPI response in these (Levin et al 2014).…”

Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model

“…These alterations are reversed specifically by antipsychotics and potentiated by psychostimulants or other pro-schizophrenia manipulations, showing predictive validity for the model Calzavara et al, 2009;Levin et al, 2011). In relation to the construct validity of the model, the SHR strain was initially developed from selecting rats from brother-sister mating of hypertensive Wistar to present a spontaneous hypertension phenotype (Okamoto and Aoki, 1963).…”