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Chunk #38 — Discussion

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Importance of GluA1 subunit-containing AMPA glutamate receptors for morphine state-dependency.
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Besides state-dependency, the current experiments also enabled to examine reward behavior in the absence of GluA1 subunit-containing AMPA receptors. No deficit in the morphine-induced place preference in GluA1−/− mice in the undrugged test situation (Sal-state) was found, suggesting that these mice are capable of learning the CS-US association and express normal place preference. Results from earlier conditioned place preference studies with GluA1−/− mice using cocaine are inconsistent, reporting either a deficit [13] or no deficit [36], [37] in the expression of cocaine-conditioned place preference. However, these results are dependent upon the design of the experiment. The deficit in place preference was only observed when using a biased apparatus with non-counterbalanced (biased) subject assignment [13], which both are factors that complicate the interpretation of the place preference data [38]. This precaution is important especially in the case of morphine that can exert anxiolytic effects [39]. The present experiments were designed to exclude the apparatus bias over the conditioning phase by inclusion of saline-saline control animals. In agreement with our findings, the pharmacological approach using AMPA receptor antagonists suggests that these receptors