title: A subpopulation of neurochemically-identified ventral tegmental area dopamine neurons is excited by intravenous cocaine.
abstract: Systemic administration of cocaine is thought to decrease the firing rates of ventral tegmental area (VTA) dopamine (DA) neurons. However, this view is based on categorizations of recorded neurons as DA neurons using preselected electrophysiological characteristics lacking neurochemical confirmation. Without applying cellular preselection, we recorded the impulse activity of VTA neurons in response to cocaine administration in anesthetized adult rats. The phenotype of recorded neurons was determined by their juxtacellular labeling and immunohistochemical detection of tyrosine hydroxylase (TH), a DA marker. We found that intravenous cocaine altered firing rates in the majority of recorded VTA neurons. Within the cocaine-responsive neurons, half of the population was excited and the other half was inhibited. Both populations had similar discharge rates and firing regularities, and most neurons did not exhibit changes in burst firing. Inhibited neurons were more abundant in the posterior VTA, whereas excited neurons were distributed evenly throughout the VTA. Cocaine-excited neurons were more likely to be excited by footshock. Within the subpopulation of TH-positive neurons, 36% were excited by cocaine and 64% were inhibited. Within the subpopulation of TH-negative neurons, 44% were excited and 28% were inhibited. Contrary to the prevailing view that all DA neurons are inhibited by cocaine, we found a subset of confirmed VTA DA neurons that is excited by systemic administration of cocaine. We provide evidence indicating that DA neurons are heterogeneous in their response to cocaine and that VTA non-DA neurons play an active role in processing systemic cocaine.
authors: Integrative Neuroscience Research Branch, Neuronal Networks Section.
authors: Carlos A
authors: http://orcid.org/0000-0002-6909-1831
authors: CA
authors: Mejias-Aponte
authors: Integrative Neuroscience Research Branch, Neuronal Networks Section.
authors: Changquan
authors: C
authors: Ye
authors: Cellular Neurobiology Research Branch, Synaptic Physiology Section, and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors: Antonello
authors: A
authors: Bonci
authors: Behavioral Neuroscience Research Branch, Behavioral Neuroscience Section, In Vivo Electrophysiology Unit, Intramural Research Program, National Institute of Drug Abuse, Baltimore, Maryland 21224, and.
authors: Eugene A
authors: EA
authors: Kiyatkin
authors: Integrative Neuroscience Research Branch, Neuronal Networks Section, mmorales@nih.gov.
authors: Marisela
authors: M
authors: Morales
mesh_terms: D000200:Action Potentials; D061605:Administration, Intravenous; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009433:Neural Inhibition; D009928:Organ Specificity; D051381:Rats; D020318:Rats, Long-Evans; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D003042:Cocaine
keywords: cocaine; in-vivo electrophysiology; intravenous; juxtacellular; single unit; ventral tegmental area
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