Involvement of glutamatergic and dopaminergic systems in the reactivity of mice to spatial and non-spatial change

Abstract

Injections of glutamatergic NMDA as well as dopaminergic antagonists produce selective place- but not cue-learning deficits in associative spatial tasks. The present work was aimed at examining if the blockade of NMDA and dopaminergic receptors interferes with the encoding of spatial information in a non-associative task specifically designed for rodents. CD1 mice injected with MK-801 (0.1 and 0.25 mg/kg), haloperidol (0.04 and 0.08 mg/kg), a combination of the lower doses of each drug (haloperidol: 0.04 mg/kg and MK-801: 0.1 mg/kg) or saline were placed in an open field containing five objects and their reactivity to the displacement (spatial change) or the substitution (non-spatial change) of some of these objects was examined. The results show that saline-injected mice reacted to spatial as to non-spatial change by increasing the time spent exploring the displaced objects or the substituted one. Both doses of MK-801 prevented mice from detecting spatial change but did not affect their reactivity to the novel object. Both doses of haloperidol abolished the reactivity of mice to spatial change but the higher dose of the drug also altered the reaction to non-spatial change. Taken together, the present results indicate that the blockade of dopaminergic or glutamatergic NMDA receptors abolishes the detection of spatial novelty. The well-documented impairing effects of haloperidol and MK-801 on spatial learning may, therefore, be the consequence of a drug-induced inability in forming and/or updating spatial representations. The effects of haloperidol was, however, less specific than that of MK-801, since haloperidol always modified activity together with the response to spatial change and, at the higher dose, abolished the detection of both spatial and non-spatial change. Finally, haloperidol pretreatment was found to enhance the effect of MK-801 thus suggesting a possible interaction between the two systems in modulating these behavioral responses.