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- Title
Opiate Exposure and Withdrawal Induces a Molecular Memory Switch in the Basolateral Amygdala between ERK1/2 and CaMKIIα-Dependent Signaling Substrates.
- Authors
Lyons, Danika; de Jaeger, Xavier; Rosen, Laura G.; Ahmad, Tasha; Lauzon, Nicole M.; Zunder, Jordan; Coolen, Lique M.; Rushlow, Walter; Laviolette, Steven R.
- Abstract
Opiate reward memories are powerful triggers for compulsive opiate-seeking behaviors. The basolateral amygdala (BLA) is an important structure for the processing of opiate-related associative memories and is functionally linked to the mesolimbic dopamine (DA) pathway. Transmission through intra-BLADAD1-like and D2-like receptors independently modulates the formation of opiate reward memories as a function of opiate-exposure state. Thus, in the opiate-naive state, intra-BLA D1 transmission is required for opiate-related memory formation. Once opiate dependence and withdrawal has developed, a functional switch to a DA D2-mediated memory mechanism takes place. However, the downstream molecular signaling events that control this functional switch between intra-BLA DA D1 versus D2 receptor transmission are not currently understood. Using an unbiased place conditioning procedure in rats combined with molecular analyses, we report that opiate rewardmemoryacquisition requires intra-BLA ERK1/2 signaling only in the previously opiate-naive state. However, following chronic opiate exposure and withdrawal, intra-BLA reward memory processing switches to a CaMKIIα-dependent memory substrate. Furthermore, the ability of intra-BLA DA D1 or D2 receptor transmission to modulate the motivational salience of opiates similarly operates through a D1-mediated ERK-dependent mechanism in the opiate-naive state, but switches to a D2-mediated CaMKIIα-dependent mechanism in the dependent/withdrawn state. Protein analysis of BLA tissue revealed a downregulation of ERK1/2 phosphorylation and a dramatic reduction in both total and phosphorylated CaMKIIα signaling, specifically in the opiate-dependent/ withdrawn state, demonstrating functional control of ERK1/2-dependent versus CaMKIIα-dependent memory mechanisms within the BLA, controlled by opiate-exposure state.
- Subjects
DRUG withdrawal symptoms; MOLECULAR memory; AMYGDALOID body; NARCOTICS; PHOSPHORYLATION; DOPAMINE
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 37, p14693
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1226-13.2013