title: 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.
authors.affiliation: Département Psychologie, Cognition et Comportement, Université de Liège, Liège, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Didone
authors.affiliation: Département Psychologie, Cognition et Comportement, Université de Liège, Liège, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Masson
authors.affiliation: Département Psychologie, Cognition et Comportement, Université de Liège, Liège, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Quoilin
authors.affiliation: Département Psychologie, Cognition et Comportement, Université de Liège, Liège, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Seutin
authors.affiliation: Département Psychologie, Cognition et Comportement, Université de Liège, Liège, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Quertemont
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects
chemical_list: D017660:Autoreceptors; D002492:Central Nervous System Depressants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D000431:Ethanol; D013469:Sulpiride
keywords: Dopamine; electrophysiology; ethanol; sensitization; ventral striatum