Role of dopaminergic system in reactivity to spatial and non-spatial changes in mice

Rationale: While experimental evidence shows that dopamine (DA) systems have an important role in locomotor function and in motivation, their role in the reactivity to spatial and non-spatial novelty is less well established. Objective: In this study, we investigated the effects of dopaminergic pharmacological manipulation on the capability of CD1 mice to encode spatial and non-spatial information in an open field with objects. Methods: The effects of systemic administration of: (1) selective D1 and D2 antagonists (SCH23390, 0.015 mg/kg or 0.020 mg/kg; sulpiride, 10 mg/kg or 20 mg/kg); (2) direct and indirect DA agonists (apomorphine, 1 mg/kg or 2 mg/kg; amphetamine, 1 mg/kg or 2 mg/kg) were studied. Results: On the one hand, systemic administration of either D1 or D2 antagonists induced a selective impairment in the detection of spatial change but did not affect reaction to non-spatial novelty. On the other hand, amphetamine induced a selective decrease in exploratory activity in the first three sessions. This decrease did not affect the ability of mice to react to spatial change, but a dose- dependent decrease was observed in reactivity to non-spatial novelty. Such an effect does not seem to be due to amphetamine-induced hyperactivity or to non-DA mechanisms, since apomorphine induced a similar neophobic profile, without affecting locomotion. Conclusions: Taken together, these results demonstrate that manipulations of DA transmission affect reactivity to spatial and non-spatial novelty. In particular, we suggest that these two behavioral responses are modulated in opposite ways by the DA system.