Extinction of Aversive Memories Associated with Morphine Withdrawal Requires ERK-Mediated Epigenetic Regulation of Brain-Derived Neurotrophic Factor Transcription in the Rat Ventromedial Prefrontal Cortex

Abstract

Recent evidence suggests that histone deacetylase (HDAC) inhibitors facilitate extinction of rewarding memory of drug taking. However, little is known about the role of chromatin modification in the extinction of aversive memory of drug withdrawal. In this study, we used conditioned place aversion (CPA), a highly sensitive model for measuring aversive memory of drug withdrawal, to investigate the role of epigenetic regulation of brain-derived neurotrophic factor (BDNF) gene expression in extinction of aversive memory. We found that CPA extinction training induced an increase in recruiting cAMP response element-binding protein (

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

“…66 However, extracellular signal-regulated protein kinase (ERK)-CREB activity is elevated during extinction of conditioned place aversion following morphine withdrawal. 67 Downstream effectors of Gα i and Gα o proteins regulate AC through phosphorylation, thereby, providing additional mechanisms for sensitization. Following activation of Gα i and Gα o , the G βγ subunit interacts with various protein kinases.…”

Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats

“…Our previous studies have revealed that the extinction of aversive memories associated with morphine withdrawal requires BDNF transcription in the rat ventromedial prefrontal cortex [24] . Because the amygdala is important for emotionassociated learning and memory, the aim of the present study was to explore whether BDNF expression in the rat amygdala was involved in the formation of aversive memories associated with conditioned morphine withdrawal.…”

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

“…Extensive experimental evidence indicates that inactivation of the mPFC either by lesion or pharmacological blockade impairs extinction of fear or drug conditioning (Hsu and Packard 2008;Wang et al 2012;Gupta et al 2013). The mPFC is known to send excitatory glutamate signals to several subcortical areas, including the amygdala, hippocampus, NAc, hypothalamus, and VTA (Frankle et al 2006;Vazquez-Borsetti et al 2009) to strengthen learning during extinction training.…”

“…ERK, in particular ERK2, is known to participate in various stages of aversive or appetitive cuedependent behavioral expression or extinction (Cestari et al 2013). Both ERK1 and ERK2 are readily phosphorylated in the NAc and dorsal striatum after acute morphine, METH, or cocaine administration (Tronson and Taylor 2007) while also evoked during morphine withdrawal or extinction in the ventral mPFC (Wang et al 2012). Suppression of ERK and CREB phosphorylation in basolateral amygdala impairs extinction of morphine withdrawal-dependent conditioned place aversion .…”