Rapid, transient synaptic plasticity in addiction

Abstract

Chronic use of addictive drugs produces enduring neuroadaptations in the corticostriatal glutamatergic brain circuitry. The nucleus accumbens (NAc), which integrates cortical information and regulates goal-directed behavior, undergoes long-term morphological and electrophysiological changes that may underlie the increased susceptibility for relapse in drug-experienced individuals even after long periods of withdrawal. Additionally, it has recently been shown that exposure to cues associated with drug use elicits rapid and transient morphological and electrophysiological changes in glutamatergic synapses in the NAc. This review highlights these dynamic drug-induced changes in this pathway that are specific to a drug seeking neuropathology, as well as how these changes impair normal information processing and thereby contribute to the uncontrollable motivation to relapse. Future directions for relapse prevention and pharmacotherapeutic targeting of the rapid, transient synaptic plasticity in relapse are discussed.

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

“…As discussed above, the NAc is a major input structure of the basal ganglia that receives inputs from many The Nucleus Accumbens: Mechanisms of Addiction brain regions (Voorn et al, 2004;Stuber et al, 2012;Britt and Bonci, 2013;Gipson et al, 2014), and the MSNs of the NAc are relatively hyperpolarized with low spontaneous activity and therefore depend on excitatory glutamatergic transmission to activate (O'Donnell and Grace, 1993;Peoples and West, 1996). Release of glutamate into the synapse causes the activation of two primary types of ionotropic glutamate receptors: the AMPARs and the NMDARs.…”

“…Afferent-and Medium Spiny Neuron-Specific Synaptic Plasticity. Being the main input structure of the ventral basal ganglia, the NAc receives glutamatergic input from multiple sources Britt and Bonci, 2013;Gipson et al, 2014), including the PFC, amygdala, hippocampus, thalamus, and VTA. However, interrogating synaptic plasticity in specific afferents or cell types of the NAc became possible only in recent years after the introduction of optogenetic (Boyden et al, 2005) and chemogenetic (Sternson and Roth, 2014) tools.…”

Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats

“…Drugs of abuse cause neural plasticity within the mesolimbic pathway, which in turn, contributes to the development and maintenance of addiction (Chen et al, 2010;Koob and Volkow, 2010;Mameli and Luscher, 2011;Feltenstein and See, 2013;Grueter et al, 2013;Gipson et al, 2014). The mesolimbic pathway regulates natural reward behaviors (Frohmader et al, 2010;Olsen, 2011;Volkow et al, 2011Volkow et al, , 2013, and repeated exposure to natural rewards causes neural plasticity similar to that induced by drugs of abuse (Solinas et al, 2008;Pitchers et al, 2010bPitchers et al, , 2013Pitchers et al, , 2014Olsen, 2011;Nader et al, 2012;Adams et al, 2013;Bardo et al, 2013), suggesting that drugs of abuse act on the same plasticity mechanisms that regulate natural reward learning (Pitchers et al, 2013(Pitchers et al, , 2014.…”

Involvement of the cerebellum in cocaine-induced memory

“…Drug experience can induce both shortand long-term plasticity mechanisms which are thought to be responsible for druginduced maladaptive behavior Kasanetz et al, 2010;Wolf, 2010;Gipson et al, 2014;Lüscher, 2016). …”

“…Currently, it is widely accepted that plasticity alterations in glutamatergic synapses regulated by dopamine and other neuromodulators as endocannabinoids result from repeated consumption of addictive drugs (Koob and Nestler, 1997;Wolf, 2010;Gipson et al, 2014;.…”