Abstract
Background: The vasopressin deficient Brattleboro (BRAT) rats have behavioral impairments which mimic those seen in other schizophrenia models. However, the mechanism by which vasopressin produces these behavioral abnormalities is unclear. Notably, elevations in dopamine signaling as well as reductions in glutamatergic signaling have been associated with behavioral impairments consistent with those observed in the BRAT rats. Therefore, a potential mechanism for vasopressin induces behavioral abnormalities could be through modulation of dopamine or glutamate signaling. Consequently, the aim of this study was to assess the modulatory function of vasopressin on dopamine and NMDA signaling. Methods: Single intraperitoneal injection of amphetamine (0.5 mg/kg), a dopamine agonist, and MK801 (0.25 mg/kg), a NMDA antagonist, were used to assess vasopressin (VP) modulatory activity on dopaminergic and glutamatergic pre-pulse inhibition of startle (PPI), social interaction and auditory event related potential (ERPs) impairments in BRAT and littermate control WT rats. Results: MK801-induced impairments were consistent and not significantly different between WT and BRAT rats suggesting minimal modulatory activity of vasopressin on NMDA signaling. In contrast, amphetamine-induced deficits were genotype dependent. In control animals, amphetamine caused a statistically significant deficit in PPI and social interaction whereas there was no effect in BRAT rats. Conversely, ERP components were unaltered in control rats, whereas N40 amplitude, evoked gamma power, and gamma signal to noise ratio were all elevated in BRAT rats. Conclusions: The ERP component analyses of BRAT rats treated with amphetamine suggest modulation of auditory information processing through interplay between dopaminergic and vasopressin. However, the behavioral and electrophysiological evidence presented here also suggest that vasopressin does not modulate glutamatergic signaling through NMDA receptors. Further evidence in necessary to determine the interaction between vasopressin and dopamine signaling and future studies are necessary to comprehend glutamatergic interactions with vasopressin that are not NMDA-mediated.
Highlights
Schizophrenia is a disabling condition which is characterized by abnormal information processing accompanied with emotional disengagement
We propose that BRAT rats will have enhanced responses to both dopaminergic and glutamatergic perturbations across behavioral and electrophysiological measures related to schizophrenia
Fisher Least Squared Differences (LSD) post hoc analyses were explored to assess differential responses between WT and BRAT rats as this was the primary rationale for the study
Summary
Schizophrenia is a disabling condition which is characterized by abnormal information processing accompanied with emotional disengagement. These deficits are manifested in conjunction with positive symptoms such as delusions and hallucinations as well as negative symptoms including anhedonia, asociality, and avolition. Current evidence supports two main theories regarding the pathophysiology of schizophrenia, which are the glutamate and dopamine hypotheses [7,8,9]. Another review suggests that functional supersensitivity of postsynaptic dopamine signaling is a common mechanism leading to positive symptoms seen in schizophrenia [16]. A potential mechanism for vasopressin induces behavioral abnormalities could be through modulation of dopamine or glutamate signaling. The aim of this study was to assess the modulatory function of vasopressin on dopamine and NMDA signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
