Impairing effect of amphetamine and concomitant ionotropic glutamate receptors blockade in the ventral striatum on spatial learning in mice

Accumulating evidence supports the involvement of the ventral striatum (VS) in spatial information processing. The multiple cortical glutamatergic and mesolimbic dopaminergic (DAergic) afferences on the same neurons in the ventral striatum provide the neuroanatomical substrate for glutamate and dopamine functional interaction. However, there is little evidence in the literature on how this interaction affects the ability to encode spatial information. First, we evaluated the effect of intra-VS bilateral infusion of different doses of amphetamine (0.3, 0.75, and 1.5 mu g/side) on the ability to detect spatial novelty in mice. Next, we examined the impact produced on the same abilities by intra-VS infusion of ineffective doses of amphetamine (0.3 mu g/side) in association with N-methyl-d-aspartate (NMDA) (3.125 ng/side) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) (0.25 ng/side) receptor antagonist. The results show that infusion of amphetamine impairs detection of spatial novelty, affecting also exploratory activity and marginally the detection of nonspatial novelty. In contrast, an association of subthreshold doses of amphetamine with NMDA or AMPA receptor antagonists exerted a selective effect on reactivity to a spatial change. These findings demonstrate that enhanced DAergic activity in the VS enhances glutamate receptor antagonist-induced impairment in learning and memory.