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Correlation between ethanol behavioral sensitization and midbrain dopamine neuron reactivity to ethanol
Author(s) -
Didone Vincent,
Masson Sébastien,
Quoilin Caroline,
Seutin Vincent,
Quertemont Etienne
Publication year - 2016
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12216
Subject(s) - ethanol , sensitization , behavioral sensitization , midbrain , dopamine , neuroscience , reactivity (psychology) , psychology , chemistry , medicine , biochemistry , central nervous system , nucleus accumbens , alternative medicine , pathology
Repeated ethanol injections lead to a sensitization of its stimulant effects in mice. Some recent results argue against a role for ventral tegmental area ( VTA ) dopamine neurons in ethanol behavioral sensitization. The aim of the present study was to test whether in vivo ethanol locomotor sensitization correlates with changes in either basal‐ or ethanol‐evoked firing rates of dopamine neurons in vitro . Female Swiss mice were daily injected with 2.5 g/kg ethanol (or saline in the control group) for 7 days and their locomotor activity was recorded. At the end of the sensitization procedure, extracellular recordings were made from dopaminergic neurons in midbrain slices from these mice. Significantly higher spontaneous basal firing rates of dopamine neurons were recorded in ethanol‐sensitized mice relative to control mice, but without correlations with the behavioral effects. The superfusion of sulpiride, a dopamine D 2 antagonist, induced a stronger increase of dopamine neuron firing rates in ethanol‐sensitized mice. This shows that the D 2 feedback in dopamine neurons is preserved after chronic ethanol administration and argues against a reduced D 2 feedback as an explanation for the increased dopamine neuron basal firing rates in ethanol‐sensitized mice. Finally, ethanol superfusion (10–100 mM) significantly increased the firing rates of dopamine neurons and this effect was of higher magnitude in ethanol‐sensitized mice. Furthermore, there were significant correlations between such a sensitization of dopamine neuron activity and ethanol behavioral sensitization. These results support the hypothesis that changes in brain dopamine neuron activity contribute to the behavioral sensitization of the stimulant effects of ethanol.