title: Diversity of Dopaminergic Neural Circuits in Response to Drug Exposure.
abstract: Addictive substances are known to increase dopaminergic signaling in the mesocorticolimbic system. The origin of this dopamine (DA) signaling originates in the ventral tegmental area (VTA), which sends afferents to various targets, including the nucleus accumbens, the medial prefrontal cortex, and the basolateral amygdala. VTA DA neurons mediate stimuli saliency and goal-directed behaviors. These neurons undergo robust drug-induced intrinsic and extrinsic synaptic mechanisms following acute and chronic drug exposure, which are part of brain-wide adaptations that ultimately lead to the transition into a drug-dependent state. Interestingly, recent investigations of the differential subpopulations of VTA DA neurons have revealed projection-specific functional roles in mediating reward, aversion, and stress. It is now critical to view drug-induced neuroadaptations from a circuit-level perspective to gain insight into how differential dopaminergic adaptations and signaling to targets of the mesocorticolimbic system mediates drug reward. This review hopes to describe the projection-specific intrinsic characteristics of these subpopulations, the differential afferent inputs onto these VTA DA neuron subpopulations, and consolidate findings of drug-induced plasticity of VTA DA neurons and highlight the importance of future projection-based studies of this system.
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Juarez
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Institute for Systems Biomedicine; Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ming-Hu
authors.initials: MH
authors.lastname: Han
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000473:pathology / Q000503:physiopathology; D017557:Ventral Tegmental Area / Q000166:cytology
chemical_list: D002491:Central Nervous System Agents; D018377:Neurotransmitter Agents; D000431:Ethanol