title: Endogenous opioid-dopamine neurotransmission underlie negative CBV fMRI signals.
abstract: Previous studies showed noxious unilateral forepaw electrical stimulation surprisingly evoked negative blood-oxygenation-level-dependent (BOLD), cerebral blood flow (CBF), and cerebral blood volume (CBV) fMRI responses in the bilateral striatum whereas the local neuronal spike and c-Fos activities increased. These negative responses are associated with vasoconstriction and appeared to override the increased hemodynamic responses that typically accompanied with increased neural activity. The current study aimed to investigate the role of μ-opioid system in modulating vasoconstriction in the striatum associated with noxious stimulation on a 4.7-Tesla MRI scanner. Specifically, we investigated: i) how morphine (a μ-opioid receptor agonist) affects the vasoconstriction in the bilateral striatum associated with noxious electrical forepaw stimulation in rats, and ii) how naloxone (an opioid receptor antagonist) and eticlopride (a dopamine D(2)/D(3) receptor antagonist) modulates the morphine effects onwards. Injection of morphine enhanced the negative striatal CBV responses to noxious stimulation. Sequential injection of naloxone in the same animals abolished the stimulus-evoked vasoconstriction. In a separate group of animals, injection of eticlopride following morphine also reduced the vasoconstriction. Our findings suggested that noxious stimulation endogenously activated opioid and dopamine receptors in the striatum and thus leading to vasoconstriction.
authors.affiliation: Department of Neurology and Biomedical Research Imaging Center, University of North Carolina, 124 Mason Farm Rd, CB#7513, Chapel Hill, NC 27599, USA. shihy@unc.edu
authors.forename: Yen-Yu I
authors.initials: YY
authors.lastname: Shih
authors.forename: Yun-Chen
authors.initials: YC
authors.lastname: Chiang
authors.forename: Bai-Chuang
authors.initials: BC
authors.lastname: Shyu
authors.forename: Fu-Shan
authors.initials: FS
authors.lastname: Jaw
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
authors.forename: Chen
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012457:Salicylamides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D012457:Salicylamides; D009270:Naloxone; D009020:Morphine; C045989:eticlopride