Correlation between ethanol behavioral sensitization and midbrain dopamine neuron reactivity to ethanol

Abstract

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 D2 antagonist, induced a stronger increase of dopamine neuron firing rates in ethanol-sensitized mice. This shows that the D2 feedback in dopamine neurons is preserved after chronic ethanol administration and argues against a reduced D2 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.

Voluntary adolescent drinking enhances excitation by low levels of alcohol in a subset of dopaminergic neurons in the ventral tegmental area

“…VTA DA neurons are clearly involved in mediating the rewarding properties of EtOH in rodents, including self-administration (Rodd et al, 2004) and EtOH-seeking behaviors (Hauser et al, 2011). EtOH has been shown to increase the firing rate of these neurons in vivo (Gessa et al, 1985; Burkhardt and Adermark, 2014) and in vitro (Brodie et al, 1990; Didone et al, 2016). …”

Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice

“…Didone et al have reported a significant positive correlation between sensitization of dopaminergic neuronal activity and behavioral sensitization induced by EtOH. 18) Because the process of sensitization to the effects of a drug is affected by the administered dose, dosing interval, and administration term, [19][20][21][22][23] we also examined EtOH-induced locomotor sensitization under different levels of illumination in the CPP box, the dependence of EtOH-induced associative learning on the administered dose, and differences in the sensitizing effects of continuous and intermittent EtOH administration.…”

Sensitization to the Stimulant Motor Effects of Ethanol Is Not Dependent On Tolerance to Ataxic or Sedative Properties of Ethanol in Female Mice

“…This common classification allows a simplified interpretation of results but has been frequently criticized because it may result in a loss of information and reduced statistical power, residual confounding and even spurious interactions [50,51]. For these reasons, we performed correlational analysis to avoid dichotomizing continuous variables and therefore optimizing our data, not to mention that this strategy has been successfully adopted in two very recent and relevant studies in the EIBS field [43,52]. This is, to our knowledge, the first time that this approach is used in a study on this topic.…”

“…This dual approach would eventually strengthen the accuracy of our results. The first sensitization score, hereafter mentioned as the "Delta Score" was calculated as [(locomotor activity on day 10) -(locomotor activity on day 1)] [13,41,43]. The second score, or "D10 Score", was the distance travelled during the 10th and last sensitization session [44,45].…”