scholarly journals Dopamine, behavior, and addiction

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Roy A. Wise ◽  
Chloe J. Jordan

AbstractAddictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning—long-term potentiation (LTP)—of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking—or “pacemaker firing”—of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.

2017 ◽  
Vol 118 (4) ◽  
pp. 1998-2008 ◽  
Author(s):  
DeNard V. Simmons ◽  
Alyssa K. Petko ◽  
Carlos A. Paladini

The in vivo firing pattern of ventral tegmental area (VTA) dopamine neurons is controlled by GABA afferents originating primarily from the nucleus accumbens (NAc), rostromedial tegmental nucleus (RMTg), and local GABA neurons within the VTA. Although different forms of plasticity have been observed from GABA inputs to VTA dopamine neurons, one dependent on cyclic GMP synthesis and the other on adenylyl cyclase activation, it is unknown whether plasticity is differentially expressed in each. Using an optogenetic strategy, we show that identified inhibitory postsynaptic currents (IPSCs) from local VTA GABA neurons and NAc afferents exhibit a cyclic GMP-dependent long-term potentiation (LTP) that is capable of inhibiting the firing activity of dopamine neurons. However, this form of LTP was not induced from RMTg afferents. Only an adenylyl cyclase-mediated increase in IPSCs was exhibited by all three inputs. Thus discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons. NEW & NOTEWORTHY We describe a mapping of plasticity expression, mediated by different mechanisms, among three distinct GABA afferents to ventral tegmental area (VTA) dopamine neurons: the rostromedial tegmental nucleus, the nucleus accumbens, and the local GABA neurons within the VTA known to synapse on VTA dopamine neurons. This work is the first demonstration that discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons.


2009 ◽  
Vol 101 (6) ◽  
pp. 2735-2737 ◽  
Author(s):  
Mitra Heshmati

Previous work has shown that a single dose of cocaine can produce long-term potentiation (LTP) of the glutamatergic synapses received by dopamine neurons in the ventral tegmental area (VTA). This and other plastic changes in the brain's reward circuitry have been suggested to underlie addiction. A recent study has provided new insights into cocaine-induced LTP, showing that it begins 3–5 h after exposure, requires activation of a dopamine D5/NMDA receptor cascade, and can be evoked by cocaine application directly to the VTA.


Neuroreport ◽  
1999 ◽  
Vol 10 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Paul G. Overton ◽  
Christopher D. Richards ◽  
Michael S. Berry ◽  
David Clark

2019 ◽  
Vol 122 (5) ◽  
pp. 643-651 ◽  
Author(s):  
Srdjan M. Joksimovic ◽  
Yukitoshi Izumi ◽  
Sonja Lj. Joksimovic ◽  
Vesna Tesic ◽  
Kathiresan Krishnan ◽  
...  

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Andon N Placzek ◽  
Gonzalo Viana Di Prisco ◽  
Sanjeev Khatiwada ◽  
Martina Sgritta ◽  
Wei Huang ◽  
...  

Recreational drug use leads to compulsive substance abuse in some individuals. Studies on animal models of drug addiction indicate that persistent long-term potentiation (LTP) of excitatory synaptic transmission onto ventral tegmental area (VTA) dopamine (DA) neurons is a critical component of sustained drug seeking. However, little is known about the mechanism regulating such long-lasting changes in synaptic strength. Previously, we identified that translational control by eIF2α phosphorylation (p-eIF2α) regulates cocaine-induced LTP in the VTA (Huang et al., 2016). Here we report that in mice with reduced p-eIF2α-mediated translation, cocaine induces persistent LTP in VTA DA neurons. Moreover, selectively inhibiting eIF2α-mediated translational control with a small molecule ISRIB, or knocking down oligophrenin-1—an mRNA whose translation is controlled by p-eIF2α—in the VTA also prolongs cocaine-induced LTP. This persistent LTP is mediated by the insertion of GluR2-lacking AMPARs. Collectively, our findings suggest that eIF2α-mediated translational control regulates the progression from transient to persistent cocaine-induced LTP.


2019 ◽  
Author(s):  
Yan-Feng Zhang ◽  
Simon D. Fisher ◽  
Manfred Oswald ◽  
Jeffery R. Wickens ◽  
John N. J. Reynolds

AbstractPauses in the firing of tonically-active cholinergic interneurons (ChIs) in the striatum coincide with phasic activation of dopamine neurons during reinforcement learning. However, how this pause influences cellular substrates of learning is unclear. Using two in vivo paradigms, we report that long-term potentiation (LTP) at corticostriatal synapses with spiny projection neurons (SPNs) is dependent on the temporal coincidence of ChI pause and dopamine phasic activation, critically accompanied by SPN depolarization.


Nature ◽  
2001 ◽  
Vol 411 (6837) ◽  
pp. 583-587 ◽  
Author(s):  
Mark A. Ungless ◽  
Jennifer L. Whistler ◽  
Robert C. Malenka ◽  
Antonello Bonci

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