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the reduction in NMDAR-mediated synaptic currents and rectify the altered NMDAR/ AMPAR ratio observed in alcohol-withdrawn rats.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.

Cannizzaro C., Talani G., Brancato A., Mulas G., Spiga S., De Luca M.A., et al. (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restores limbic memory loss, dendritic spine structure, and NMDAR-dependent LTD in the nucleus accumbens of alcohol-withdrawn rats.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(5), 929-943 [10.1523/JNEUROSCI.1377-18.2018].

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restores limbic memory loss, dendritic spine structure, and NMDAR-dependent LTD in the nucleus accumbens of alcohol-withdrawn rats

Cannizzaro C.;Brancato A.;
2019-01-01

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.
2019
Settore BIO/14 - Farmacologia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382989/
Cannizzaro C., Talani G., Brancato A., Mulas G., Spiga S., De Luca M.A., et al. (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(5), 929-943 [10.1523/JNEUROSCI.1377-18.2018].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/366280
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