| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Talani, Giuseppe Masala, Nicola Fois, Giulia R. Muggironi, Giulia Diana, Marco Mulas, Giovanna Sanna, Enrico Biggio, Giovanni Licheri, Valentina Spiga, Saturnino Cannizzaro, Carla |
| Description |
Author Affiliation: Spiga S ( Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy); Talani G ( Institute of Neuroscience, National Research Council, Monserrato, 09042 Cagliari, Italy); Mulas G ( Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy); Licheri V ( Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy); Fois GR ( 'G. Minardi' Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.); Muggironi G ( 'G. Minardi' Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.); Masala N ( Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy); Cannizzaro C ( Department of Sciences for Health Promotion, University of Palermo, 90127 Palermo, Italy); Biggio G ( Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy); Sanna E ( Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy); Diana M ( 'G. Minardi' Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy dsfdiana@uniss.it.); |
| 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. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
35 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-09-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Alcoholism Physiopathology Dendritic Spines Physiology Ethanol Pharmacology Long-Term Synaptic Depression Nucleus Accumbens Animals Central Nervous System Depressants Dopaminergic Neurons Glutamic Acid Neuronal Plasticity Organ Culture Techniques Rats, Wistar Synaptic Transmission Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
