RODENT MODELS OF SCHIZOPHRENIA-LIKE SYMPTOMS INCREASE POLYDIPSIA

Abstract

Primary polydipsia, excessive drinking without known medical cause, continues to occur with a significant prevalence in psychiatric populations. While the etiology of polydipsia remains unknown, the fact that it is significantly associated with a diagnosis of schizophrenia has led some to postulate that the two may share common neurological pathophysiologies. Animal models of schizophrenia-like symptoms have focused on modeling the core behavioral and neurochemical features of the illness, like cognitive deficits and enhanced dopamine transmission. Here, we used three well-established models, including repeated amphetamine treatment, subchronic MK-801 (an N-methyl-D-aspartate [NMDA]-receptor antagonist), and post-weaning social isolation. We also examined a “double-hit” model, combining NMDA-receptor antagonism and social isolation. We paired these models to test the hypothesis that drinking will be enhanced in a paradigm of excessive drinking in the rat. In rodents, non-physiologic drinking can be induced by intermittent presentation of food (e.g., one sugar-pellet a minute) in the presence of a drinking spout to a hungry animal, termed schedule-induced polydipsia (SIP). Animals pretreated with pharmacological or non-pharmacological models of schizophrenia-like symptoms showed significantly increased SIP, The “double hit” model did not further increase drinking above that of either social isolation or MK-801 treatment alone. A moderate amount of spontaneous polydipsia in the homecage of MK-801-treated rats was also observed and resulted in one death secondary to excessive drinking, a phenomenon also found in inpatients with schizophrenia. Following repeated treatment with AMPH, there was some evidence that over time, animals learned to drink increased amounts independently of the scheduled food presentation. This evidence suggests that the excessive drinking behavior observed in polydipsia associated with schizophrenia may have a learned component. In summary, animal models of schizophrenia-like symptoms augmented SIP behavior, showing that polydipsia associated with schizophrenia may be modeled in rodents. As each model has been shown to modify dopamine transmission to some degree, the evidence suggests augmented SIP may reflect changes in dopamine transmission and dopamine may be the common link between polydipsia and schizophrenia. Further research is necessary to fully elucidate the mechanisms underlying SIP, polydipsia and schizophrenia.