Variable prenatal stress results in impairments of sustained attention and inhibitory response control in a 5-choice serial reaction time task in rats

Abstract

Rats repeatedly exposed to variable prenatal stress (PNS) exhibit schizophrenia-like behavioral signs such as social withdrawal, elevations in amphetamine-induced locomotor activity, deficits in sensory-motor gating, as well as impairments in memory-related task performance. However, to date there have been no studies designed to test the hypothesis that variable PNS would lead to disruptions in sustained attention and inhibitory response control (i.e., symptoms also commonly observed in schizophrenia and other neuropsychiatric disorders such as attention-deficit hyperactivity disorder). In the current study, the effects of variable PNS in rats were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a 5-choice serial reaction time task (5C-SRTT). In a separate series of experiments, the glutamate (N-methyl-d-aspartate [NMDA]) antagonist, MK-801 (0.025–0.05mg/kg), and the norepinephrine reuptake inhibitor, atomoxetine (0.30–3.0mg/kg), were administered acutely to assess the sensitivity of PNS subjects to glutamatergic and noradrenergic manipulations. The results indicated that exposure to variable PNS significantly impaired accuracy in the VSD version of the 5C-SRTT and increased premature and timeout responses in the VITI version. In addition, both doses of MK-801 impaired accuracy, increased premature and timeout responses in PNS, but not control subjects. In contrast, atomoxetine decreased premature and timeout responses in both PNS and control subjects in the VITI version of the task and improved accuracy in the PNS subjects. The results suggest that exposure to variable PNS in rats results in impairments of sustained attention and inhibitory response control and that these deficits can be exacerbated by NMDA antagonism and improved by a norepinephrine uptake inhibitor. Collectively, these data further support the premise that variable PNS in rats is a valid model system for the study of neuropsychiatric disorders and their treatment.