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Cell-type specific synaptic plasticity in dorsal striatum is associated with punishment-resistance compulsive-like cocaine self-administration in mice

Published inNeuropsychopharmacology, vol. 48, no. 3, p. 448-458
Publication date2023-02
First online date2022-09-07
Abstract

Addiction-related compulsion-like behavior can be modeled in rodents with drug self-administration (SA) despite harmful consequences. Recent studies suggest that the potentiation of glutamatergic transmission at the orbitofrontal cortex (OFC) to dorsal striatum (DS) synapses drives the transition from controlled to compulsion-like SA. However, the timing of the induction of this synaptic plasticity remains elusive. Here, mice were first allowed to intravenously self-administer cocaine. When mice had to endure a risk of electrical foot shock, only a fraction persevered in cocaine SA. In these persevering mice, we recorded high A/N ratios (AMPA-R/NMDA-R: α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor) in both types of spiny projection neurons (i.e., D1 and D2 dopamine receptor-expressing SPNs). By contrast, when we prepared slices at the end of the acquisition period, in all mice, the A/N was high in D1R- but not D2R-SPNs. These results indicate that the transition to compulsion-like cocaine SA emerges during the punishment sessions, where synapses onto D2R-SPNs are strengthened. In renouncing individuals, the cocaine-evoked strengthening in D1R-SPNs is lost. Our study thus reveals the cell-type specific sequence of the induction of plasticity that eventually may cause compulsion-like SA.

eng
Keywords
  • Mice
  • Animals
  • Cocaine
  • Punishment
  • Nucleus Accumbens / metabolism
  • Neuronal Plasticity / physiology
  • Behavior, Addictive
  • Receptors, Dopamine D1 / metabolism
Citation (ISO format)
PASCOLI, Vincent Jean et al. Cell-type specific synaptic plasticity in dorsal striatum is associated with punishment-resistance compulsive-like cocaine self-administration in mice. In: Neuropsychopharmacology, 2023, vol. 48, n° 3, p. 448–458. doi: 10.1038/s41386-022-01429-8
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ISSN of the journal0893-133X
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