Dopamine D1 receptors are not critical for opiate reward but can mediate opiate memory retrieval in a state-dependent manner

• D1 receptor homozygous knockout mice demonstrate normal morphine place preferences.
• Blocking rat basolateral amygdala (BLA) D1 receptors during training inhibits this preference.
• Blocking BLA D1 receptors during both training and testing restores this preference.
• This suggests that BLA D1 receptors mediate state-dependent memory retrieval.

Although D1 receptor knockout mice demonstrate normal morphine place preferences, antagonism of basolateral amygdala (BLA) D1 receptors only during drug-naive rat conditioning has been reported to inhibit the expression of a morphine place preference. One possible explanation for this result is state-dependent learning. That is, the omission of the intra-BLA infusion cue during testing — which acts as a potent discriminative stimulus — may have prevented the recall of a morphine–environment association and therefore, the consequent expression of a morphine place preference. To examine this possibility, we tested whether intra-BLA infusion of the D1-receptor antagonist SCH23390 during both training and testing might reveal a morphine place preference. Our results suggest that in previously drug-naive animals, D1 receptor antagonism during testing restores the opiate conditioned place preference that is normally absent when D1 receptors are blocked only during training, suggesting that BLA D1 receptors can mediate state-dependent memory retrieval.