Rapid Synaptogenesis in the Nucleus Accumbens Is Induced by a Single Cocaine Administration and Stabilized by Mitogen-Activated Protein Kinase Interacting Kinase-1 Activity

Abstract

Our study originally demonstrates that a single administration of cocaine is able to induce stable synaptic rewiring in the nucleus accumbens, which will likely influence responses to subsequent drug exposure. It also unravels a new functional role for cocaine-induced extracellular signal-regulated kinase pathway independently of nuclear targets. Finally, it reveals that mitogen-activated protein kinase interacting kinase-1 has a pivotal role in cocaine-induced connectivity.

Dopamine and addiction: what have we learned from 40 years of research

“…On the contrary, chronic alcohol (Zhou et al 2007) and morphine (Robinson and Kolb 1999), decrease the spine density in the NAc. These structural changes, initially described in response to repeated administration of drugs, have also been found after a single administration of cocaine (Dos Santos et al 2017). Interestingly, abstinence from drug has also been shown to produce alterations in dendritic spines that may participate in the withdrawal symptoms and the negative affect state that characterize this phase of addiction (Spiga et al 2014a).…”

“…Striatal structural changes in MSNs induced by drugs are mediated, at least in part, by DA. Indeed, structural changes found in culture of MSNs or in vivo after administration of cocaine depend on increases in the extracellular DA concentration(Fasano et al 2013;Martin et al 2011) and the stimulation of DA receptors (DosSantos et al 2017;Ren et al 2010;Zhang et al 2012). The increase in the density of dendritic spines observed after cocaine exposure was initially reported in both D1Rand D2R-expressing DA neurons but appears to be more durable in D1R-expressing neurons(Lee et al 2006).…”

Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity

“…Structural and functional plasticity of synapses are the fundamental mechanisms that underlie addiction even though the role of actin in this process remains controversial 2,11,30,97 . Acute or chronic cocaine exposure, as well as abstinence, facilitates dendritic spine outgrowth and spine density in reward-related brain regions such as prefrontal cortex and nucleus accumbens 31,32,92,98,99 . Our previous study established a role of Cyfip2, a component of the WAVE regulatory complex that mediates branched actin formation.…”

Neurophysiological and neuropsychological damages produced by cocaine in adult populations

“…Cocaine consumption already has pandemic characteristics, due to its powerful excitatory effects on the central nervous system, causing that when there is a strong dependence on this drug, relapses oblige the consumer to engage in behaviors that damage their family environment, their emotional environment, their work environment and their social environment to achieve them. 8 Neural communication known as synapsis occurs by two modalities: excitation or inhibition, which is severely altered in cocaine use. If the functional connectivity in the brain is altered, the basic and superior psychological processes will obviously be altered.…”