ORIGINAL INVESTIGATION Impairing effect of amphetamine and concomitant ionotropic glutamate receptors blockade in the ventral striatum on spatial learning in mice Roberto Coccurello & Alberto Oliverio & Andrea Mele Received: 30 May 2012 / Accepted: 15 January 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Rationale Accumulating evidence supports the involvement of the ventral striatum (VS) in spatial information processing. The multiple cortical glutamatergic and mesolimbic dopami- nergic (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. Objective First, we evaluated the effect of intra-VS bilateral infusion of different doses of amphetamine (0.3, 0.75, and 1.5 μg/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 μg/side) in association with N-methyl-D-aspartate (NMDA) (3.125 ng/side) or α-amino-3-hydroxy-5-methyli- soxazole-4-propionic acid (AMPA) (0.25 ng/side) receptor antagonist. Results The results show that infusion of amphetamine impairs detection of spatial novelty, affecting also explor- atory 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. Conclusions These findings demonstrate that enhanced DAergic activity in the VS enhances glutamate receptor antagonist-induced impairment in learning and memory. Keywords Amphetamine . NMDA receptors . AMPA receptors . Ventral striatum . Spatial information . Signal-to-noise ratio Introduction The ventral striatum (VS) is traditionally viewed as a neural interface between the limbic and the motor system (Mogenson et al. 1980), subserving action selection, appetitive learning, and motivated goal-oriented behaviors (Ikemoto and Panksepp 1999; Kelley 2004). Nevertheless, the existence of converging inputs from brain regions known to be involved in spatial information processing, such as the ventral subiculum, the entorhinal, and perirhinal cortices (Smith and Bolam 1990; Groenewegen et al. 1999), supports the view that this structure may also play a role in the encoding and storage of spatial information. This hypothesis is sustained by behavioral evi- dence demonstrating that lesions and neuropharmacological manipulation of the VS impair performance of laboratory rodents in several spatial learning tasks (Annett et al. 1989; Sutherland and Rodriguez 1989; Usiello et al. 1998; Smith- Roe et al. 1999; Setlow and McGaugh 1998; Roullet et al. 2001; Coccurello et al. 2012). The VS is constituted by a small number of cell types. GABAergic medium-sized spiny neurons (MSNs) account for nearly 95 % of VS cell population. These cells receive conver- gent mesolimbic dopamine (DA) and corticolimbic glutamate (GLU) inputs (Bouyer et al. 1984; Kawaguchi 1997; Smith et al. 1994; Pickel et al. 1996; Aizman et al. 2000; Sesack et al. R. Coccurello : A. Oliverio : A. Mele Department of Biology and Biotechnology, Università degli Studi di Roma “La Sapienza”, P.le Aldo Moro 5, 00185 Rome, Italy R. Coccurello : A. Oliverio : A. Mele C.N.R. National Research Council of Italy (Cell Biology and Neurobiology Institute (IBCN)), Rome, Italy A. Oliverio : A. Mele (*) Centro di Ricerca in Neurobiologia D. Bovet, Università degli Studi di Roma “La Sapienza”, P.le Aldo Moro 5, 00185 Rome, Italy e-mail: andrea.mele@uniroma1.it Psychopharmacology DOI 10.1007/s00213-013-2989-9