Effects of pharmacological inhibition of dopamine receptors on memory load capacity

Memory capacity (MC) refers to the limited capacity of working memory and is defined as the number of elements that an individual can remember for a short retention interval. MC is impaired in many human pathologies, such as schizophrenia and ageing. Fronto-striatal dopamine regulates working memory, through its action on dopamine D1- and D2-like receptors. Human and rodent studies have suggested that MC is improved by D2 dopamine receptor agonists. Although D1 receptors have been crucially involved in the maintenance of working memory during delay, their role in regulating the capacity of WM remains poorly explored. In this study, we tested the effects of systemic injection of the D1-like and D2-like receptor antagonists, SCH 23390 and Haloperidol respectively, on MC in mice. For this, we used a modified version of the object recognition task, the Different/Identical Objects Task (DOT/IOT), which allows the evaluation of MC in rodents. The results showed a negative interaction between the dose of both drugs and the number of objects that could be remembered. The doses of SCH 23390 and Haloperidol that impaired novel object discrimination in the highest memory load condition were about 4 and 3 time lower, respectively, of those impairing performance in the lowest memory load condition. However, while SCH 23390 specifically impaired memory load capacity, the effects of Haloperidol were associated to impairment in exploratory behaviors. These findings may help to predict the cognitive side effects induced by Haloperidol in healthy subjects.