Early Adolescent Emergence of Reversal Learning Impairments in Isolation-Reared Rats.

Cognitive impairments appear early in the progression of schizophrenia, often preceding the symptoms of psychosis. Thus, the systems subserving these functions may be more vulnerable to, and mechanistically linked with, the initial pathology. Understanding the trajectory of behavioral and anatomical abnormalities relevant to the schizophrenia prodrome and their sensitivity to interventions in relevant models will be critical to identifying early therapeutic strategies. Isolation rearing of rats is an environmental perturbation that deprives rodents of social contact from weaning through adulthood and produces behavioral and neuronal abnormalities that mirror some pathophysiology associated with schizophrenia, e.g. frontal cortex abnormalities and prepulse inhibition (PPI) of startle deficits. Previously, we showed that PPI deficits in isolation-reared rats emerge in mid-adolescence (4 weeks after weaning; approx. postnatal day 52) but are not present when tested at 2 weeks after weaning (approx. postnatal day 38). Because cognitive deficits are reported during early adolescence, are relevant to the prodrome, and are linked to functional outcome, we examined the putative time course of reversal learning deficits in isolation-reared rats. Separate groups of male Sprague Dawley rats were tested in a two-choice discrimination task at 2 and 8 weeks after weaning, on postnatal day 38 and 80, respectively. The isolation-reared rats displayed impaired reversal learning at both time points. Isolation rearing was also associated with deficits in PPI at 4 and 10 weeks after weaning. The reversal learning deficits in the isolated rats were accompanied by reductions in parvalbumin immunoreactivity, a marker for specific subpopulations of GABAergic neurons, in the hippocampus. Hence, isolation rearing of rats may offer a unique model to examine the ontogeny of behavioral and neurobiological alterations that may be relevant to preclinical models of prodromal psychosis.