Identification of a Dopamine Receptor-Mediated Opiate Reward Memory Switch in the Basolateral Amygdala–Nucleus Accumbens Circuit

Abstract

The basolateral amygdala (BLA), ventral tegmental area (VTA), and nucleus accumbens (NAc) play central roles in the processing of opiate-related associative reward learning and memory. The BLA receives innervation from dopaminergic fibers originating in the VTA, and both dopamine (DA) D1 and D2 receptors are expressed in this region. Using a combination of in vivo single-unit extracellular recording in the NAc combined with behavioral pharmacology studies, we have identified a double dissociation in the functional roles of DA D1 versus D2 receptor transmission in the BLA, which depends on opiate exposure state; thus, in previously opiate-naive rats, blockade of intra-BLA D1, but not D2, receptor transmission blocked the acquisition of associative opiate reward memory, measured in an unbiased conditioned place preference procedure. In direct contrast, in rats made opiate dependent and conditioned in a state of withdrawal, intra-BLA D2, but not D1, receptor blockade blocked opiate reward encoding. This functional switch was dependent on cAMP signaling as comodulation of intra-BLA cAMP levels reversed or replicated the functional effects of intra-BLA D1 or D2 transmission during opiate reward processing. Single-unit in vivo extracellular recordings performed in neurons of the NAc confirmed an opiate-statedependent role for BLA D1/D2 transmission in NAc neuronal response patterns to morphine. Our results characterize and identify a novel opiate addiction switching mechanism directly in the BLA that can control the processing of opiate reward information as a direct function of opiate exposure state via D1 or D2 receptor signaling substrates.

Glutamate Mechanisms Underlying Opiate Memories

“…1a). The BLA-shell projection has also been implicated in morphine reward (Lintas et al 2011). In this study, dopamine receptor antagonists in the BLAwere capable of altering neurophysiological responses of shell neurons to morphine (Lintas et al 2011).…”

“…The BLA-shell projection has also been implicated in morphine reward (Lintas et al 2011). In this study, dopamine receptor antagonists in the BLAwere capable of altering neurophysiological responses of shell neurons to morphine (Lintas et al 2011). The BLA potentiates shell neuronal activity in part via stimulation of NMDA-Rs (Floresco et al 1998;Floresco et al 2001).…”

Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

“…Furthermore, animal studies have shown that D1R antagonism blocks nicotine motivation in nondependent mice (36). A recent study showed that blockade of D1R but not D2R transmission prevented acquisition of opiate-reward memory in nondependent rats, and D2R but not D1R blockade prevented opiate-reward encoding in dependent and withdrawn rats (37). However, previous studies suggest that both acute nicotine and opiate reward are mediated by the non-DAergic brainstem tegmental pedunculopontine (TPP) nucleus (9,12,21), and thus must involve separate cells in the TPP that are thought to mediate burst-firing of VTA DA neurons (5, 14); burst-firing that we show here is involved in the response to acute nicotine.…”

Molecular Changes in Opioid Addiction: The Role of Adenylyl Cyclase and cAMP/PKA System

“…113,114 In particular, the pyramidal neurons of the basolateral amygdala receive input from the VTA. In saline-treated amygdala slices, DA reduced the amplitude of excitatory postsynaptic currents (EPSCs) by inhibiting α-amino-3-hydroxy-5-mehtyl-4-isoxazoleproprionic acid (AMPA) receptors.…”