title: Differential effects of natural rewards and pain on vesicular glutamate transporter expression in the nucleus accumbens.
abstract: BACKGROUND
  Pain and natural rewards such as food elicit different behavioral effects. Both pain and rewards, however, have been shown to alter synaptic activities in the nucleus accumbens (NAc), a key component of the brain reward system. Mechanisms by which external stimuli regulate plasticity at NAc synapses are largely unexplored. Medium spiny neurons (MSNs) from the NAc receive excitatory glutamatergic inputs and modulatory dopaminergic and cholinergic inputs from a variety of cortical and subcortical structures. Glutamate inputs to the NAc arise primarily from prefrontal cortex, thalamus, amygdala, and hippocampus, and different glutamate projections provide distinct synaptic and ultimately behavioral functions. The family of vesicular glutamate transporters (VGLUTs 1-3) plays a key role in the uploading of glutamate into synaptic vesicles. VGLUT1-3 isoforms have distinct expression patterns in the brain, but the effects of external stimuli on their expression patterns have not been studied.
  
  
  RESULTS
  In this study, we use a sucrose self-administration paradigm for natural rewards, and spared nerve injury (SNI) model for chronic pain. We examine the levels of VGLUTs (1-3) in synaptoneurosomes of the NAc in these two behavioral models. We find that chronic pain leads to a decrease of VGLUT1, likely reflecting decreased projections from the cortex. Pain also decreases VGLUT3 levels, likely representing a decrease in projections from GABAergic, serotonergic, and/or cholinergic interneurons. In contrast, chronic consumption of sucrose increases VGLUT3 in the NAc, possibly reflecting an increase from these interneuron projections.
  
  
  CONCLUSIONS
  Our study shows that natural rewards and pain have distinct effects on the VGLUT expression pattern in the NAc, indicating that glutamate inputs to the NAc are differentially modulated by rewards and pain.
authors.affiliation: Department of Biochemistry, New York University School of Medicine, New York, New York, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Tukey
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Eberle
authors.forename: Yossef
authors.initials: Y
authors.lastname: Goffer
authors.forename: Toby R
authors.initials: TR
authors.lastname: Manders
authors.forename: Edward B
authors.initials: EB
authors.lastname: Ziff
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009417:Nerve Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D013395:Sucrose / Q000494:pharmacology; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
chemical_list: D050496:Vesicular Glutamate Transport Proteins; D013395:Sucrose