PMID- 1336704
OWN - NLM
STAT- MEDLINE
DCOM- 19930225
LR  - 20190613
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 598
IP  - 1-2
DP  - 1992 Dec 11
TI  - Activation of locus coeruleus neurons by nucleus paragigantocellularis or noxious 
      sensory stimulation is mediated by intracoerulear excitatory amino acid 
      neurotransmission.
PG  - 185-95
AB  - The nucleus paragigantocellularis (PGi), located in the rostral ventrolateral 
      medulla, is one of two major afferents to the nucleus locus coeruleus (LC). 
      Electrical stimulation of PGi exerts a robust, predominantly excitatory influence 
      on LC neurons that is blocked by intracerebroventricular (i.c.v.) administration 
      of the broad spectrum excitatory amino acid (EAA) antagonists kynurenic acid 
      (KYN) or gamma-D-glutamylglycine (DGG), but not by the selective 
      N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-7-phosphonoheptanoate 
      (AP7). I.c.v. injection of KYN or DGG also blocked activation of LC neurons 
      evoked by noxious somatosensory stimuli. These results indicate that activation 
      of LC neurons by PGi and noxious stimuli may be mediated by an EAA acting at a 
      non-NMDA receptor in LC. In the present study, microiontophoretic techniques were 
      used to determine the sensitivity of LC neurons in vivo to the selective EAA 
      receptor agonists kainate (KA), NMDA and quisqualate (QUIS). Microinfusion and 
      microiontophoresis were also used to determine whether direct application of KYN, 
      the preferential non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3 
      dione (CNQX) or the selective NMDA receptor antagonist 
      2-amino-5-phosphonovalerate (AP5) onto LC neurons blocked excitation elicited by 
      stimulation of PGi or the sciatic nerve. The results demonstrated that individual 
      LC neurons were robustly activated by direct application of KA, NMDA and QUIS. 
      Iontophoretically applied KYN reduced or completely antagonized responses evoked 
      by all 3 agonists. In contrast, iontophoretically applied AP5 strongly attenuated 
      NMDA-evoked excitation, while KA-and QUIS-evoked responses were not affected by 
      this agent. Furthermore, direct application of KYN or the specific non-NMDA 
      receptor antagonist, CNQX, onto LC neurons substantially attenuated or completely 
      blocked synaptic activation produced by PGi or sciatic nerve stimulation in 
      nearly every LC neuron tested. Microinfusion of the selective NMDA receptor 
      antagonist AP5 had no effect on sciatic nerve-evoked responses. These results 
      confirm our hypothesis that activation of LC neurons from PGi is mediated by an 
      EAA operating primarily at a non-NMDA receptor subtype on LC neurons. 
      Furthermore, these findings provide additional support for the hypothesis that 
      this pathway mediates at least some sensory-evoked responses of LC neurons.
FAU - Ennis, M
AU  - Ennis M
AD  - Department of Anatomy and Cell Biology, University of Cincinnati College of 
      Medicine, OH 45267-0521.
FAU - Aston-Jones, G
AU  - Aston-Jones G
FAU - Shiekhattar, R
AU  - Shiekhattar R
LA  - eng
GR  - DA06214/DA/NIDA NIH HHS/United States
GR  - HL08097/HL/NHLBI NIH HHS/United States
GR  - NS24698/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amino Acids)
SB  - IM
MH  - Amino Acids/antagonists & inhibitors/*physiology
MH  - Animals
MH  - Electric Stimulation
MH  - Iontophoresis
MH  - Locus Coeruleus/cytology/*physiology
MH  - Male
MH  - Medulla Oblongata/*physiology
MH  - Neurons/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sensory Receptor Cells/*drug effects
MH  - Synapses/physiology
MH  - Synaptic Transmission/*drug effects
EDAT- 1992/12/11 00:00
MHDA- 1992/12/11 00:01
CRDT- 1992/12/11 00:00
PHST- 1992/12/11 00:00 [pubmed]
PHST- 1992/12/11 00:01 [medline]
PHST- 1992/12/11 00:00 [entrez]
AID - 0006-8993(92)90182-9 [pii]
AID - 10.1016/0006-8993(92)90182-9 [doi]
PST - ppublish
SO  - Brain Res. 1992 Dec 11;598(1-2):185-95. doi: 10.1016/0006-8993(92)90182-9.