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

Spiga, Saturnino and Talani, Giuseppe and Mulas, Giovanna and Licheri, Valentina and Fois, Giulia R. and Muggironi, Giulia and Masala, Nicola and Cannizzaro, Carla and Biggio, Giovanni and Sanna, Enrico and Diana, Marco (2014) Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats. Proceedings of The National Academy of Sciences, Vol. 111 (35), p. E3745-E3754. eISSN 1091-6490. Article.

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DOI: 10.1073/pnas.1406768111

Abstract

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-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-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

Item Type:Article
ID Code:10360
Status:Published
Refereed:Yes
Uncontrolled Keywords:Dopamine, synaptic plasticity, Golgi, glutamate
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
Publisher:The National Academy of Sciences of the USA
eISSN:1091-6490
Deposited On:24 Nov 2014 09:25

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