Systems Level Neuroplasticity in Drug Addiction

Abstract

Drug addiction is a chronic relapsing disorder for which research has been dedicated to understand the various factors that contribute to development, loss of control, and persistence of compulsive addictive behaviors. In this review, we provide a broad overview of various theories of addiction, drugs of abuse, and the neurobiology involved across the addiction cycle. Specific focus is devoted to the role of the mesolimbic pathway in acute drug reinforcement and occasional drug use, the mesocortical pathway and associated areas (e.g., the dorsal striatum) in escalation/dependence, and the involvement of these pathways and associated circuits in mediating conditioned responses, drug craving, and loss of behavioral control thought to underlie withdrawal and relapse. With a better understanding of the neurobiological factors that underlie drug addiction, continued preclinical and clinical research will aid in the development of novel therapeutic interventions that can serve as effective long-term treatment strategies for drug-dependent individuals.

Synaptic mechanisms underlying persistent cocaine craving

“…Supporting this, utilizing a higher dose of cocaine (which led to incubation of craving) elicited elevation of CP-AMPAR levels in IL-D1R MSN shell and BLA-D2R MSN shell pathways, although the behavioral consequences of the CP-AMPAR plasticity were not tested 19 . Future studies should investigate the BLA-NAc core pathway, as this BLA output is most strongly implicated in cue-induced cocaine seeking 59, 60 .…”

Risky Decision Making, Prefrontal Cortex, and Mesocorticolimbic Functional Connectivity in Methamphetamine Dependence

“…The mesocorticolimbic system, originating in the midbrain ventral tegmental area (VTA) and projecting to the nucleus accumbens, amygdala, hippocampus and medial PFC 18 , substantially influences goal-directed behaviors, and pathological drug-seeking behavior may result from drug-induced changes in this circuitry 18, 19 . Studies using resting-state functional connectivity (RSFC) to assess temporal correlations of spontaneous regional activity when participants are at rest 20 have identified abnormalities in connectivity between nodes of the mesocorticolimbic system in cocaine and opiate users 18 .…”

“…Studies using resting-state functional connectivity (RSFC) to assess temporal correlations of spontaneous regional activity when participants are at rest 20 have identified abnormalities in connectivity between nodes of the mesocorticolimbic system in cocaine and opiate users 18 . However, PFC and striatal dysfunction during risky decision-making by substance-dependent individuals 21 has not been linked directly to network activity, nor has it yet been examined in methamphetamine users.…”

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.…”