Poor inhibitory control and neurochemical differences in high compulsive drinker rats selected by schedule-induced polydipsia

Rationale Schedule-induced polydipsia (SIP), characterized by the development of excessive drinking under intermittent food reinforcement schedules, has been proposed as a model for obsessive-compulsive disorder, schizophrenia and drug abuse. Objectives The purpose of this study is to investigate if individual differences in SIP reflect psychopathological behavioural traits related to lack of inhibitory control and reactivity to novelty, and if these differences have neurochemical correlates. Methods Outbred Wistar rats were selected for being either high (HD) or low (LD) drinkers according to their SIP behaviour. We tested locomotor reactivity to a novel environment and inhibitory control on the five-choice serial reaction time task (5-CSRTT), under baseline vs. extinction conditions and following challenge with d-amphetamine (saline, 0.5 or 1 mg/kg). Post-mortem analyses of the monoaminergic levels in different brain regions were also analysed. Results Compared to LD animals, HD rats exhibiting SIP acquisition showed no differences in spontaneous locomotor reactivity to novelty. On the 5-CSRTT, HD rats showed a greater increase in perseverative responses under extinction, a trend towards elevated premature responses on baseline, and a significantly greater elevation of premature responses to d-amphetamine 0.5 mg/kg. The HD animals also exhibited increased serotonin activity in the amygdala, and correlational analyses between the rate of drinking on SIP and monoamine levels also revealed altered dopaminergic mesolimbic function. Conclusions These findings show that HD rats selected by SIP exhibit compulsive and impulsive behaviour based on measures of performance on the five-choice serial reaction time task and associated with changes in monoaminergic systems in limbic-striatal circuitry.