title: Locus of onset and subpopulation specificity of in vivo ethanol effect in the reciprocal ventral tegmental area-nucleus accumbens circuit.
abstract: Elevated levels of dopamine in the nucleus accumbens (nAc) as a consequence of increased activation of dopaminergic neurons in the VTA are associated with the reinforcing properties of ethanol consumption, but whether the initiation of drug-response is connected to a direct activation of dopaminergic cell bodies in the VTA region or involves GABAergic neurons in VTA and/or the nAc is unclear. To this end, neuronal firing rate was recorded simultaneously in the VTA and nAc of awake and freely-moving C57BL6/J mice receiving an intraperitoneal (i.p.) injection of ethanol (0.75, 2.0, or 3.5g/kg) or saline. Recorded units were classified based on electrophysiological properties and the pharmacological response to the dopamine D2 receptor agonist quinpirole into putative dopaminergic (DA) neurons and fast-spiking or slow-spiking putative GABAergic neurons. Our data show that ethanol acutely decreases the firing frequency of GABAergic units in both the VTA and nAc in a dose-dependent manner, and enhances the firing rate of DA neurons. In order to define the onset of ethanol-induced rate changes normalized population vectors describing the collective firing rate of classes of neurons over time were generated and compared with saline-treatment. Population vectors of DA neurons in the VTA and GABAergic units in the nAc showed a significant deviation from the saline condition within 40s following ethanol-administration (2.0g/kg), while inhibition of GABAergic units in the VTA had a slower onset. In conclusion, the data presented here suggests that EtOH exerts a direct effect on DA firing frequency, but that decreased firing frequency of inhibitory neurons in VTA and nAc contributes to the dopamine-elevating properties of ethanol.
authors: Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway; Champalimaud Neuroscience Programme, Champalimaud Center for the Unknown, Lisbon, Portugal.
authors: John M
authors: JM
authors: Burkhardt
authors: Addiction Biology Unit, Institute of Neuroscience and Physiology, Gothenburg University, Sweden. Electronic address: louise.adermark@neuro.gu.se.
authors: Louise
authors: L
authors: Adermark
mesh_terms: D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D000431:Ethanol
keywords: Alcohol; Dopamine; Electrophysiology; GABA; Medium spiny neurons; Reward