Molecular and neuronal plasticity mechanisms in the amygdala-prefrontal cortical circuit: implications for opiate addiction memory formation.

Laura G Rosen,Ninglei Sun,Steven R Laviolette,Walter Rushlow

doi:10.3389/fnins.2015.00399

Laura G Rosen, Ninglei Sun + Show 2 more

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https://doi.org/10.3389/fnins.2015.00399

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Journal: Frontiers in neuroscience	Publication Date: Nov 5, 2015
Citations: 28	License type: cc-by

Affiliation: Western University

Abstract

The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related “trigger” memories that may persist for lengthy periods of time, even during abstinence, in both humans, and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall, and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC) and basolateral nucleus of the amygdala (BLA) share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway's ventral tegmental area (VTA) and nucleus accumbens (NAc) and can modulate dopamine (DA) transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modeling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK) and the Ca2+/calmodulin-dependent protein kinases (CaMK). Evidence will be reviewed that points to the importance of critical molecular memory switches within the mammalian brain that might mediate the neuropathological adaptations resulting from chronic opiate exposure, dependence, and withdrawal.

Highlights

The persistent and compulsive behavioral patterns associated with opiate addiction depend largely on the ability of opiateclass drugs to produce powerful associative memories linked to their intense, euphorigenic properties
How do early, acute drug-experiences become encoded in the brains emotional memory circuits? Once chronic exposure and dependence have developed, do separate neuronal or molecular memory substrates come online during the processing of addiction-related memory? Do these neural memory adaptations lead to increased resistance and/or increased motivational salience linked to drug-associated cues? Adding to the complexity of addiction-related memory processing is the recognition that distinct phases of learning and memory involve different molecular and neuroanatomical substrates
To examine the potential molecular substrates controlling the effects of chronic opiate exposure and withdrawal on BLAdependent associative opiate reward memory formation, Lyons et al (2013) performed a series of molecular and behavioral studies in rats investigating the effects of opiate exposure state on expression levels and functional roles of intra-basolateral amygdala (BLA) extracellular-signal-regulated kinase system (ERK) 1/2 and CaMKII signaling pathways during associative opiate reward memory formation

Summary

Introduction

The persistent and compulsive behavioral patterns associated with opiate addiction depend largely on the ability of opiateclass drugs to produce powerful associative memories linked to their intense, euphorigenic properties. In follow-up studies, it was reported that intra-BLA transmission through either DA D1 or D2 receptor substrates could control the acquisition of associative opiate reward memories, and regulate the motivational salience of opiaterelated reward memories via functional interactions with the NAc. infusions of either selective D1R or D2R agonists directly into the BLA was shown to strongly increase the reward salience of normally sub-reward threshold conditioning doses of morphine, again, measured in a place conditioning procedure (Lintas et al, 2012).

Results

Conclusion