Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons.

Abstract

In people with a prior history of opioid misuse, cues associated with previous drug intake can trigger relapse even after years of abstinence. Examining the processes that lead to the formation and maintenance of the memories between cues/context and the opioid may help to discover new therapeutic candidates to treat drug-seeking behavior. The hippocampus is a brain region essential for learning and memory, which has been involved in the mechanisms underlying opioid cravings. The formation of memories and associations are thought to be dependent on synaptic strengthening associated with structural plasticity of dendritic spines. Here, we assess how dendritic spines in the CA1 region of the hippocampus are affected by morphine-conditioning training. Our results show that morphine pairing with environmental cues (ie, the conditioned place preference (CPP) apparatus) triggers a significant decrease in the number of thin dendritic spines in the hippocampus. Interestingly, this effect was observed regardless of the expression of a conditioned response when mice were trained using an unpaired morphine CPP design and was absent when morphine was administered in the home cage. To investigate the mechanism underlying this structural plasticity, we examined the role of Rho GTPase in dendritic spine remodeling. We found that synaptic expression of RhoA increased with morphine conditioning and blocking RhoA signaling prevented the expression of morphine-induced CPP. Our findings uncover novel mechanisms in response to morphine-associated environmental cues and the underlying alterations in spine plasticity.