Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling

By C. Lüscher, R. Malenka. Neuron, 2011

1,075 citations recorded by the source corpus.

Addictive drugs have in common that they target the mesocoticolimbic dopamine (DA) system. This system originates in the ventral tegmental area (VTA) and projects mainly to the nucleus accumbens (NAc) and prefrontal cortex (PFC). Here we review the effects that such drugs leave on glutamatergic and GABAergic synaptic transmission in these three brain areas. We refer to these changes as drug-evoked synaptic plasticity, which outlasts the presence of the drug in the brain and contributes to the reorganization of neural circuits. While in most cases these early changes are not sufficient to induce the disease, with repetitive drug exposure, they may add up and cause addictive behavior.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/3a30f4b8b94b59db47c95e7c97069630c223861d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Malenka
2. S. Lammel
3. K. Tye
4. B. Lim
5. C. Lüscher
6. Karl Deisseroth
7. Seth M. Tomchik
8. Lisa Scheunemann

In Cognitive Neuroscience

1. S. Lammel
2. R. Malenka
3. B. Lim
4. K. Tye
5. C. Lüscher
6. Seth M. Tomchik
7. Karl Deisseroth
8. S. Hyman

Citations in the corpus

• Reward and aversion in a heterogeneous midbrain dopamine system (2013, background): “…by many investigators that drugs of abuse hijack the brain’s “reward system” and that among the most important neural circuit modifications that contribute to the development of addiction are changes in the properties of excitatory synapses on midbrain VTA DA neurons (Luscher and Malenka 2011).”
• Activation of VTA GABA neurons disrupts reward consumption (2012, neutral): “…Area (VTA) is a heterogeneous brain structure containing neuronal populations that are essential for the expression of motivated behaviors and actions related to addiction and other neuropsychiatric illnesses (Fields et al., 2007; Luscher and Malenka, 2011; Nestler and Carlezon, 2006; Wise, 2004).”
• Postsynaptic plasticity of cholinergic synapses underlies the induction and expression of appetitive and familiarity memories in Drosophila (2022, result): “Consistent with previous reports (Dubnau et  al., 2001; McGuire et  al., 2001; Schwaerzel et  al., 2002), a slight drop in aversive memory performance (Figure 1a) was not statistically different from their genetic controls, and also observable in the permissive temperature controls (23°C; see…”
• Dopaminergic neurons encode a distributed, asymmetric representation of temperature in Drosophila (2013, background): “…variety of behaviors in animals, including learning (Wise, 2004; Davis, 2011), arousal (Andretic et al., 2005), motor control (Hauber, 1998), motivation (Wise, 2004), addiction and obesity (Kenny, 2011; Lüscher and Malenka, 2011), and salience-based decisionmaking (Zhang et al., 2007; Doya, 2008).”
• GABA Neurons of the VTA Drive Conditioned Place Aversion (2012, background): “DA is thought to represent a teaching signal and has also been implicated in the induction of addictive behaviors (Lüscher and Malenka, 2011).”