Abstract
Glutamatergic AMPA and NMDA receptors in the ventral tegmental area (VTA) are central for cocaine first exposure and posterior craving maintenance. However, the exact rules that coordinate the synaptic dynamics of these receptors in dopaminergic VTA neurons and behavioral outcomes are poorly understood. Additionally, synaptic homeostatic plasticity is present in response to chronic excitability changes in neuronal circuits, adjusting the strength of synapses to stabilize the firing rate. Despite having correspondent mechanisms, little is known about the relationship between continuous cocaine exposure and homeostatic synaptic changes in the VTA neurons. Here, we assess the role of homeostatic mechanisms in the neurobiology of cocaine addiction by providing a brief overview of the parallels between cocaine-induced synaptic potentiation and long-term synaptic adaptations, focusing on the regulation of GluA1- and GluN1- containing receptors.
Highlights
Dopaminergic projections originated in the ventral tegmental area (VTA) are critical for reward learning and, drug abuse behaviors [5, 19, 23]
A central hypothesis is that these craving phenotypes reflect greater incentive motivation for the drug and associated stimuli [21] mediated by the potentiation of glutamatergic synapses on VTA dopamine neurons [13]
These rats take longer to reach the breaking point and earn more cocaine injections when compared to controls. Extinction of this behavior was impaired, and the reinstatement of the drug-paired lever response was facilitated. These counterintuitive results could only be explained after studying the influence of homeostatic regulations due to the continuous change in neuronal excitability induced by the transient manipulation of GluN1-NMDA receptor (NMDAR) in VTA
Summary
Dopaminergic projections originated in the ventral tegmental area (VTA) are critical for reward learning and, drug abuse behaviors [5, 19, 23]. VTA dopamine neurons exhibit transient NMDA receptor (NMDAR)dependent increases in AMPA receptor (AMPAR)-mediated currents following either single or repeated cocaine This article considers recent evidence on the influence of synaptic potentiation and subsequent homeostatic regulation in the VTA into behavioral outcomes of cocaine craving after chronic drug exposure.
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