Abstract
The GluA1 subunit of the AMPA receptor has been implicated in anhedonia. Mice that lack GluA1 (Gria1 knockout mice) show reduced lick cluster size, a measure of palatability in feeding behaviour. This deficit may reflect a role for GluA1 in encoding the hedonic value of palatable substances or instead a role for GluA1 in the behavioural expression of hedonic value. We tested the role of GluA1 in hedonic value by assessing sensitivity to changes in the rewarding property of sucrose as a consequence of negative/positive contrast effects in female mice. During training, on half of the days consumption of a flavour (CS+) mixed with 4% sucrose was preceded by consumption of 1% sucrose (positive contrast). On the other half of days consumption of a different flavour (CS–) mixed with 4% sucrose was preceded by consumption of 16% sucrose (negative contrast). In the test session both wild-type, controls and Gria1 knockout mice consumed more of the CS+ flavour than the CS– flavour. While Gria1 knockout mice showed reduced lick cluster sizes, both genotypes made larger lick clusters for the CS+ flavour than the CS– flavour suggesting that the CS+ was more palatable than the CS–. A follow up experiment in normal mice demonstrated that the negative contrast procedure resulted in a conditioned reduction of palatability of the CS– in comparison to an associatively neutral, novel flavour. The results failed to demonstrate a role for GluA1 in hedonic value suggesting that, instead, GluA1 is necessary for hedonic responding.
Highlights
In line with the glutamatergic hypothesis of schizophrenia [1], Gria1, the gene that encodes for the GluA1 subunit of the AMPA receptor for glutamate, has genome wide association to schizophrenia [2, 3]
As a consequence of the sucrose adaptation procedure in Experiment 1 we found that mice consumed less of the conditioned stimulus (CS)– flavour than CS+ flavour during training
In the first period of access consumption of 16% sucrose was greater than 1% sucrose (Fig. 1a, F(1,24) = 406.23, p< .001, ηp2 = 0.944, 90% CI[.89,.96])
Summary
In line with the glutamatergic hypothesis of schizophrenia [1], Gria, the gene that encodes for the GluA1 subunit of the AMPA receptor for glutamate, has genome wide association to schizophrenia [2, 3]. This supports previous post-mortem work that found a reduction in hippo campal GluA1 mRNA[4, 5], and GluA1 [6]and AMPA binding sites [7]in schizophrenia patients. In order to test the role of Gria in anhedonia, Austen, Sprengel, and Sanderson [10] examined the effect of GluA1 deletion on consumption of sucrose. Lick cluster size, a measure of palatability, was reduced in Gria1− /− mice
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