title: Opioid modulation of ventral pallidal afferents to ventral tegmental area neurons.
abstract: Activation of mu opioid receptors within the ventral tegmental area (VTA) can produce reward through the inhibition of GABAergic inputs. GABAergic neurons in the ventral pallidum (VP) provide a major input to VTA neurons. To determine the specific VTA neuronal targets of VP afferents and their sensitivity to mu opioid receptor agonists, we virally expressed channel rhodopsin (ChR2) in rat VP neurons and optogenetically activated their terminals in the VTA. Light activation of VP neuron terminals elicited GABAergic IPSCs in both dopamine (DA) and non-DA VTA neurons, and these IPSCs were inhibited by the mu opioid receptor agonist DAMGO. In addition, using a fluorescent retrograde marker to identify VTA-projecting VP neurons, we found them to be hyperpolarized by DAMGO. Both of these actions decrease GABAergic input onto VTA neurons, revealing two mechanisms by which endogenous or exogenous opioids can activate VTA neurons, including DA neurons.
authors.affiliation: Ernest Gallo Clinic and Research Center, Wheeler Center for the Neurobiology of Addiction, and Department of Neurology, University of California, San Francisco, Emeryville, California 94608, USA. gregh@gallo.ucsf.edu
authors.forename: Gregory O
authors.initials: GO
authors.lastname: Hjelmstad
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Xia
authors.forename: Elyssa B
authors.initials: EB
authors.lastname: Margolis
authors.forename: Howard L
authors.initials: HL
authors.lastname: Fields
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000075402:Channelrhodopsins; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D005917:Globus Pallidus / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D062308:Optogenetics / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D000075402:Channelrhodopsins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-