Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Carla Cannizzaro, Giulia Muggironi, Marco Diana, Enrico Sanna, Valentina Licheri, Giulia R. Fois, Nicola Masala, Giuseppe Talani, Saturnino Spiga, Giovanna Mulas, Giovanni Biggio

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62 Citazioni (Scopus)


Alcoholism involves long-term cognitive deficits, including memoryimpairment, resulting in substantial cost to society. Neuronalrefinement and stabilization are hypothesized to confer resilienceto poor decision making and addictive-like behaviors, such asexcessive ethanol drinking and dependence. Accordingly, structuralabnormalities are likely to contribute to synaptic dysfunctionsthat occur from suddenly ceasing the use of alcohol afterchronic ingestion. Here we show that ethanol-dependent ratsdisplay a loss of dendritic spines in medium spiny neurons of thenucleus accumbens (Nacc) shell, accompanied by a reduction oftyrosine hydroxylase immunostaining and postsynaptic density95-positive elements. Further analysis indicates that “long thin”but not “mushroom” spines are selectively affected. In addition,patch-clamp experiments from Nacc slices reveal that long-termdepression (LTD) formation is hampered, with parallel changes infield potential recordings and reductions in NMDA-mediated synapticcurrents. These changes are restricted to the withdrawalphase of ethanol dependence, suggesting their relevance in thegenesis of signs and/or symptoms affecting ethanol withdrawaland thus the whole addictive cycle. Overall, these results highlightthe key role of dynamic alterations in dendritic spines and theirpresynaptic afferents in the evolution of alcohol dependence. Furthermore,they suggest that the selective loss of long thin spinestogether with a reduced NMDA receptor function may affectlearning. Disruption of this LTD could contribute to the rigid emotionaland motivational state observed in alcohol dependence.
Lingua originaleEnglish
pagine (da-a)3745-3754
Numero di pagine10
RivistaProceedings of the National Academy of Sciences of the United States of America
Stato di pubblicazionePublished - 2014

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