The GluA1 subunit of the AMPA receptor has been implicated in schizophrenia. While GluA1 is important for cognition, it is not clear what the role of GluA1 is in hedonic responses that are relevant to the negative symptoms of disorders such as schizophrenia. Here, we tested mice that lack GluA1 (Gria1 -/- mice) on consumption of sucrose solutions using a licking microstructure analysis. GluA1 deletion drastically reduced palatability (as measured by the mean lick cluster size) across a range of sucrose concentrations. Although initial lick rates were reduced, measures of consumption across long periods of access to sucrose solutions were not affected by GluA1 deletion and Gria1 -/- mice showed normal satiety responses to high sucrose concentrations. GluA1 deletion also failed to impair flavour conditioning, in which increased intake of a flavour occurred as a consequence of prior pairing with a high sucrose concentration. These results demonstrate that GluA1 plays a role in responding on the basis of palatability rather than other properties, such as the automatic and learnt post-ingestive, nutritional consequences of sucrose. Therefore, Gria1 -/- mice provide a potential model of anhedonia, adding converging evidence to the role of glutamatergic dysfunction in various symptoms of schizophrenia and related disorders.

The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in schizophrenia. Gria1 knockout in mice results in recently experienced stimuli acquiring aberrantly high salience. This suggests that GluA1 may be important for learning that is sensitive to the temporal contiguity between events. To test this, mice were trained on a Pavlovian trace conditioning procedure in which the presentation of an auditory cue and food were separated by a temporal interval. Wild-type mice initially learnt, but with prolonged training came to withhold responding during the trace-conditioned cue, responding less than for another cue that was nonreinforced. Gria1 knockout mice, in contrast, showed sustained performance over training, responding more to the trace-conditioned cue than the nonreinforced cue. Therefore, the trace-conditioned cue acquired inhibitory properties (signalling the absence of food) in wild-type mice, but Gria1 deletion impaired the acquisition of inhibition, thus maintaining the stimulus as an excitatory predictor of food. Furthermore, when there was no trace both groups showed successful learning. These results suggest that cognitive abnormalities in disorders like schizophrenia in which gluatamatergic signalling is implicated may be caused by aberrant salience leading to a change in the nature of the information that is encoded.