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Rewiring of Prelimbic Inputs to the Nucleus Accumbens Core Underlies Cocaine-Induced Behavioral Sensitization.

Authors :
Kwon, Jaehan
Kim, Hyun Jin
Lee, Hyoung-Ro
Ho, Won-Kyung
Kim, Joung-Hun
Lee, Suk-Ho
Source :
Biological Psychiatry. Sep2023, Vol. 94 Issue 5, p378-392. 15p.
Publication Year :
2023

Abstract

Unbalanced activity of medium spiny neurons (MSNs) of the direct and indirect pathways mediates reward-related behaviors induced by addictive drugs. Prelimbic (PL) input to MSNs in the nucleus accumbens core (NAcC) plays a key role in cocaine-induced early locomotor sensitization (LS). However, the adaptive plastic changes at PL-to-NAcC synapses underlying early LS remain unclear. Using transgenic mice and retrograde tracing, we identified NAcC-projecting pyramidal neurons (PNs) in the PL cortex based on the expression of dopamine receptor types (D1R or D2R). To examine cocaine-induced alterations in PL-to-NAcC synapses, we measured excitatory postsynaptic current amplitudes evoked by optostimulation of PL afferents to MSNs. Riluzole was chosen to test the effects of PL excitability on cocaine-induced changes of PL-to-NAcC synapses. NAcC-projecting PNs were segregated into D1R- and D2R-expressing PNs (D1- and D2-PNs, respectively), and their excitability was opposingly regulated by respective dopamine agonists. Both D1- and D2-PNs exhibited balanced innervation of direct MSNs and indirect MSNs in naïve animals. Repeated cocaine injections resulted in biased synaptic strength toward direct MSNs through presynaptic mechanisms in both D1- and D2-PNs, although D2R activation reduced the D2-PN excitability. Under group 1 metabotropic glutamate receptors coactivation, however, D2R activation enhanced the D2-PN excitability. The cocaine-induced rewiring accompanied LS, and both rewiring and LS were precluded by PL infusion of riluzole, which reduced the intrinsic excitability of PL neurons. These findings indicate that cocaine-induced rewiring of PL-to-NAcC synapses correlates well with early behavioral sensitization and that rewiring and LS can be prevented by riluzole-induced reduction of excitability of PL neurons. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00063223
Volume :
94
Issue :
5
Database :
Academic Search Index
Journal :
Biological Psychiatry
Publication Type :
Academic Journal
Accession number :
167304995
Full Text :
https://doi.org/10.1016/j.biopsych.2022.12.024