Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats. VTA glutamatergic projections to the nucleus accumbens suppress psychostimulant-seeking behavior.

Featured Paper of the Month – November 2024

Published in Neuropsychopharmacology by Flavia Barbano and Marisela Morales, et al. of the NIDA IRP Neuronal Networks Section.

Summary

The mesocorticolimbic dopamine system is essential for psychostimulant-related behaviors like conditioned place preference (CPP), self-administration, and relapse after extinction. Centered on dopamine neurons in the ventral tegmental area (VTA) and their connections to the nucleus accumbens (NAc), this system drives psychostimulant reward responses. Our study shows that activating a parallel VTA-originating glutamatergic pathway targeting the NAc shell can suppress psychostimulant-seeking behavior. Activation of the VTA-NAc glutamatergic pathway did not affect cocaine CPP acquisition but blocked the expression, stress- and priming-induced reinstatement of cocaine and methamphetamine CPP, and cocaine-seeking in a self-administration model. Unlike the dopamine system, this VTA-NAc glutamatergic pathway suppresses psychostimulant-seeking, presenting a potential target for reducing relapse in psychostimulant users.

Publication Information

Barbano, M Flavia; Qi, Jia; Chen, Emma; Mohammad, Uzma; Espinoza, Orlando; Candido, Marcos; Wang, Huiling; Liu, Bing; Hahn, Suyun; Vautier, François; Morales, Marisela

VTA glutamatergic projections to the nucleus accumbens suppress psychostimulant-seeking behavior Journal Article

In: Neuropsychopharmacology, vol. 49, no. 12, pp. 1905–1915, 2024, ISSN: 1740-634X.

Abstract | Links

@article{pmid38926603,

title = {VTA glutamatergic projections to the nucleus accumbens suppress psychostimulant-seeking behavior},

author = {M Flavia Barbano and Jia Qi and Emma Chen and Uzma Mohammad and Orlando Espinoza and Marcos Candido and Huiling Wang and Bing Liu and Suyun Hahn and François Vautier and Marisela Morales},

url = {https://pubmed.ncbi.nlm.nih.gov/38926603/},

doi = {10.1038/s41386-024-01905-3},

issn = {1740-634X},

year  = {2024},

date = {2024-11-01},

urldate = {2024-11-01},

journal = {Neuropsychopharmacology},

volume = {49},

number = {12},

pages = {1905--1915},

abstract = {Converging evidence indicates that both dopamine and glutamate neurotransmission within the nucleus accumbens (NAc) play a role in psychostimulant self-administration and relapse in rodent models. Increased NAc dopamine release from ventral tegmental area (VTA) inputs is critical to psychostimulant self-administration and NAc glutamate release from prelimbic prefrontal cortex (PFC) inputs synapsing on medium spiny neurons (MSNs) is critical to reinstatement of psychostimulant-seeking after extinction. The regulation of the activity of MSNs by VTA dopamine inputs has been extensively studied, and recent findings have demonstrated that VTA glutamate neurons target the NAc medial shell. Here, we determined whether the mesoaccumbal glutamatergic pathway plays a role in psychostimulant conditioned place preference and self-administration in mice. We used optogenetics to induce NAc release of glutamate from VTA inputs during the acquisition, expression, and reinstatement phases of cocaine- or methamphetamine-induced conditioned place preference (CPP), and during priming-induced reinstatement of cocaine-seeking behavior. We found that NAc medial shell release of glutamate resulting from the activation of VTA glutamatergic fibers did not affect the acquisition of cocaine-induced CPP, but it blocked the expression, stress- and priming-induced reinstatement of cocaine- and methamphetamine CPP, as well as it blocked the priming-induced reinstatement of cocaine-seeking behavior after extinction. These findings indicate that in contrast to the well-recognized mesoaccumbal dopamine system that is critical to psychostimulant reward and relapse, there is a parallel mesoaccumbal glutamatergic system that suppresses reward and psychostimulant-seeking behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}