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

ABSTRACT: 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.

SUBMITTER: Ting-A-Kee R

PROVIDER: S-EPMC3773936 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

Ting-A-Kee Ryan R Mercuriano Laura E LE Vargas-Perez Hector H George Susan R SR van der Kooy Derek D

Behavioural brain research 20130326

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 asso ...[more]

PMID: 23538064

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Project description:Stressful life events induce abnormalities in emotional and cognitive behaviour. The endogenous opioid system plays an essential role in stress adaptation and coping strategies. In particular, the µ-opioid receptor (?R), one of the major opioid receptors, strongly influences memory processing in that alterations in ?R signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether ?R signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective ?R depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal ?R signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal ?Rs were significantly activated during acute stress. Blockage of hippocampal ?Rs, non-selective deletion of ?Rs or selective deletion of ?Rs on GABAergic neurons (?RGABA) reversed EP-stress-induced impairment of memory retrieval, with no effect on the elevation of serum corticosterone after stress. Electrophysiological results demonstrated that stress depressed hippocampal GABAergic synaptic transmission to CA1 pyramidal neurons, thereby leading to excitation/inhibition (E/I) imbalance in a ?RGABA-dependent manner. Pharmaceutically enhancing hippocampal GABAA receptor-mediated inhibitory currents in stressed mice restored their memory retrieval, whereas inhibiting those currents in the unstressed mice mimicked the stress-induced impairment of memory retrieval. Our findings reveal a novel pathway in which endogenous opioids recruited by acute stress predominantly activate ?RGABA to depress GABAergic inhibitory effects on CA1 pyramidal neurons, which subsequently alters the E/I balance in the hippocampus and results in impairment of memory retrieval.

Dataset Information

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

Publications

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

Similar Datasets

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