Abstract
Immediate early genes (IEGs) were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN) subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.
Highlights
Immediate early genes (IEGs) are activated transiently and rapidly throughout the brain by many cellular stimuli including psychostimulants
While studies examining psychostimulant-mediated IEG function in dopamine receptor 1 (D1)-medium spiny neuron (MSN) vs. dopamine receptor 2 (D2)-MSN subtypes are sparse, they have provided some insight into mechanisms by which IEGs act in these neuron subtypes
Overall we focus on three select IEGs that have been examined in MSN subtypes in psychostimulant action
Summary
Immediate early genes (IEGs) are activated transiently and rapidly throughout the brain by many cellular stimuli including psychostimulants. Use of Cre-inducible herpes simplex virus (HSV) to overexpress ∆FosB in D1-MSNs in the NAc of D1-Cre mice confirmed the enhanced cocaine-mediated behavioral responses and showed that ∆FosB alone can enhance immature spine formation and reduce AMPAR/NMDAR ratios, in D1-MSNs (Grueter et al, 2013; Table 1). These structural and synaptic plasticity changes by ∆FosB are an indication of enhanced silent synapses, which are characteristic of cocaine effects on D1-MSNs (Graziane et al, 2016). Previous rat studies demonstrate c-Fos induction in both MSN subtypes when a psychostimulant is given in a novel environment
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