Short communicationObject recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice

- Heterozygous mice for dopamine transporter (DAT+/−) exhibit higher levels of synaptic dopamine.
- Here we confirmed that D2 antagonism can interfere in object recognition.
- We observed in DAT+/− a natural phenotype of impaired novel object memory recognition.
- The injection of haloperidol at 0.05 mg before object exposition restored object recognition.
- This effect could be explained by restoring D2 activity to optimal levels, acting on memory acquisition.

Genetically-modified mice without the dopamine transporter (DAT) are hyperdopaminergic, and serve as models for studies of addiction, mania and hyperactive disorders. Here we investigated the capacity for object recognition in mildly hyperdopaminergic mice heterozygous for DAT (DAT +/−), with synaptic dopaminergic levels situated between those shown by DAT −/− homozygous and wild-type (WT) mice. We used a classical dopamine D2 antagonist, haloperidol, to modulate the levels of dopaminergic transmission in a dose-dependent manner, before or after exploring novel objects. In comparison with WT mice, DAT +/− mice showed a deficit in object recognition upon subsequent testing 24 h later. This deficit was compensated by a single 0.05 mg/kg haloperidol injection 30 min before training. In all mice, a 0.3 mg/kg haloperidol injected immediately after training impaired object recognition. The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity.