Dopamine restores limbic memory loss, dendritic spine structure, and NMDAR-dependent LTD in the nucleus accumbens of alcohol-withdrawn rats

Carla Cannizzaro, Anna Brancato, Marco Diana, Enrico Sanna, Rosa Anna Maria Marino, Giuseppe Talani, Saturnino Spiga, Angela Sanna, Giovanna Mulas, Giovanni Biggio, Maria Antonietta De Luca

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4 Citazioni (Scopus)

Abstract

Alcohol abuse leads to aberrant forms of emotionally salient memory, i.e., limbic memory, that promote escalated alcohol consumption and relapse. Accordingly, activity-dependent structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing chronic alcohol consumption. Here we show that alcohol-dependent male rats fail to perform an emotional-learning task during abstinence but recover their functioning by L -3,4-dihydroxyphenylalanin ( L -DOPA) administration during early withdrawal. L -DOPA also reverses the selective loss of dendritic “long thin” spines observed in medium spiny neurons of the nucleus accumbens (NAc) shell of alcohol-dependent rats during abstinence, as well as the reduction in tyrosine hydroxylase immunostaining and postsynaptic density-95-positive elements. Patch-clamp experiments in NAc slices reveal that both in vivo systemic L -DOPA administration and in vitro exposure to dopamine can restore the loss of long-term depression (LTD) formation, counteract the reduction in NMDAR-mediated synaptic currents and rectify the altered NMDAR/ AMPAR ratio observed in alcohol-withdrawn rats. Further, in vivo microdialysis experiments show that blunted dopaminergic signaling is revivedafter L -DOPAtreatment during early withdrawal. These results suggest a key role of anefficient dopamine signaling for maintaining, and restore, neural trophism, NMDA-dependent LTD, and ultimately optimal learning.
Lingua originaleEnglish
pagine (da-a)929-943
Numero di pagine15
RivistaTHE JOURNAL OF NEUROSCIENCE
Volume39
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Cannizzaro, C., Brancato, A., Diana, M., Sanna, E., Marino, R. A. M., Talani, G., Spiga, S., Sanna, A., Mulas, G., Biggio, G., & De Luca, M. A. (2019). Dopamine restores limbic memory loss, dendritic spine structure, and NMDAR-dependent LTD in the nucleus accumbens of alcohol-withdrawn rats. THE JOURNAL OF NEUROSCIENCE, 39, 929-943.