title: Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.
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.
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy;
authors.forename: Saturnino
authors.initials: S
authors.lastname: Spiga
authors.affiliation: Institute of Neuroscience, National Research Council, Monserrato, 09042 Cagliari, Italy;
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talani
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy; Department of Sciences for Health Promotion, University of Palermo, 90127 Palermo, Italy; and.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mulas
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy;
authors.forename: Valentina
authors.initials: V
authors.lastname: Licheri
authors.affiliation: "G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.
authors.forename: Giulia R
authors.initials: GR
authors.lastname: Fois
authors.affiliation: "G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Muggironi
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy;
authors.forename: Nicola
authors.initials: N
authors.lastname: Masala
authors.affiliation: Department of Sciences for Health Promotion, University of Palermo, 90127 Palermo, Italy; and.
authors.forename: Carla
authors.initials: C
authors.lastname: Cannizzaro
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy; Institute of Neuroscience, National Research Council, Monserrato, 09042 Cagliari, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, 09126 Cagliari, Italy; Institute of Neuroscience, National Research Council, Monserrato, 09042 Cagliari, Italy;
authors.forename: Enrico
authors.initials: E
authors.lastname: Sanna
authors.affiliation: "G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy dsfdiana@uniss.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Diana
mesh_terms: D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D049229:Dendritic Spines / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D009714:Nucleus Accumbens / Q000503:physiopathology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D018698:Glutamic Acid
keywords: Golgi; dopamine; glutamate; synaptic plasticity