title: Separate GABA afferents to dopamine neurons mediate acute action of opioids, development of tolerance, and expression of withdrawal.
abstract: GABA release from interneurons in VTA, projections from the nucleus accumbens (NAc), and rostromedial tegmental nucleus (RMTg) was selectively activated in rat brain slices. The inhibition induced by μ-opioid agonists was pathway dependent. Morphine induced a 46% inhibition of IPSCs evoked from the RMTg, 18% from NAc, and IPSCs evoked from VTA interneurons were almost insensitive (11% inhibition). In vivo morphine treatment resulted in tolerance to the inhibition of RMTg, but not local interneurons or NAc, inputs. One common sign of opioid withdrawal is an increase in adenosine-dependent inhibition. IPSCs evoked from the NAc were potently inhibited by activation of presynaptic adenosine receptors, whereas IPSCs evoked from RMTg were not changed. Blockade of adenosine receptors selectively increased IPSCs evoked from the NAc during morphine withdrawal. Thus, the acute action of opioids, the development of tolerance, and the expression of withdrawal are mediated by separate GABA afferents to dopamine neurons.
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Matsui
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Brooke C
authors.initials: BC
authors.lastname: Jarvie
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Brooks G
authors.initials: BG
authors.lastname: Robinson
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Shane T
authors.initials: ST
authors.lastname: Hentges
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: williamj@ohsu.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Williams
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D057967:Infusions, Intraventricular; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D005680:gamma-Aminobutyric Acid