Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex

• DOI: 10.1523/jneurosci.3113-17.2018
• Publication Date: 2018-04-23T16:15:13Z
• Authors: Jing Jing Li; Hanna Szkudlarek; Justine Renard; Roger Hudson; Walter Rushlow; Steven R. Laviolette
• Keywords: emotional memory; Male; Narcotics; MAP Kinase Signaling System; fear memory; 150; ventral tegmental area; Prefrontal Cortex; polymorphism; Rats, Sprague-Dawley; Cell and Developmental Biology; 03 medical and health sciences; 0302 clinical medicine; Reward; Memory; Animals; prefrontal cortex; Morphine; Receptors, Dopamine D1; signal-regulated kinase; Receptors, Dopamine D4; Ventral Tegmental Area; transmission; opioids; PTSD; signal-regulated kinase; basolateral amygdala; prelimbic cortex; differentially modulate; homeostatic regulation; emotional memory; Fear; differentially modulate; Posttraumatic-stress-disorder; Rats; 3. Good health; Dopamine Agonists; Mental Recall; prelimbic cortex; homeostatic regulation; Conditioning, Operant; dopamine; Anatomy; heroin; basolateral amygdala

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience normally nonsalient memories, whereas D1 (D1Rs) demonstrated selectively block recall reward- or aversion-related associative memories. In present study, using a combination fear conditioning opiate reward male rats, we examined role D4/D1R signaling during processing fear-related acquisition subsequent sensitivity formation. We report that D4R activation potentiates subthreshold cues simultaneously rewarding effects systemic intra-ventral tegmental area (VTA) morphine cues. contrast, blocking salient memories with intra-PFC D1R activation, blocks ability intra-VTA place preference. These were dependent upon dissociable phosphorylation states calcium-calmodulin-kinase II extracellular signal-related kinase 1-2, following respectively. Together, these findings reveal new insights into how aberrant DAergic associated downstream molecular pathways may modulate concomitantly increase addiction vulnerability.SIGNIFICANCE STATEMENT Post-traumatic is highly comorbid this use translational model examine receptors, cortex (PFC), differentially control mechanisms might regulate opioids. demonstrate not only controls acquisition, but receptor prevents potentiation effects. novel account for disturbances addictive liability opioid-class drugs.