Role of norepinephrine in the interaction between the lateral reticular nucleus and the nucleus raphe magnus: an electrophysiological and behavioral study.
We have previously demonstrated that the nucleus raphe magnus (NRM) sends a predominantly inhibitory projection to the lateral reticular nucleus (LRN); however, the pharmacology of this pathway is not known. The purpose of this study was to examine the role of norepinephrine in the NRM-LRN system using both electrophysiological and behavioral techniques. Sixty-nine LRN cells were recorded extracellularly. Cells were tested for their response to noxious and innocuous peripheral stimulation applied to the dorsal body surface. The majority of cells were classified as wide dynamic range, with inhibition being the predominant response; receptive fields were located primarily on the tail and hind limbs. The effect of excitatory amino acid glutamate (GLU) administration into NRM (GLU-NRM) was tested on all 69 cells. GLU-NRM inhibited 55 of 69 LRN cells tested; 7 cells were excited and 7 cells did not respond. Thirty-nine LRN cells were tested for their response to norepinephrine (NE) iontophoretically applied in LRN (NE-LRN). Two distinct types of effects were noted. In 9 cells, both NE-LRN and GLU-NRM produced a strong inhibition, with the magnitude of effect between the 2 drugs significantly correlated. In a second group of cells (n = 12), GLU-NRM produced an inhibitory effect while NE-LRN had no effect on the cells' baseline firing rate. However, when the 2 drugs were applied simultaneously, NE-LRN blocked the inhibitory effects of NRM stimulation. The effect of the alpha 2-receptor antagonist yohimbine (YOH) on NRM-evoked responses was tested in 30 LRN cells. The majority of these cells were inhibited by GLU-NRM. Similar to the dichotomous effect noted by NE-LRN, YOH applied iontophoretically in LRN (YOH-LRN) had two predominant effects on NRM-produced inhibition. In 14 of 27 cells, YOH-LRN significantly potentiated the inhibitory effects of NRM stimulation by increasing the duration of the inhibitory epoch an average of 100 sec. In 7 of 27 cells, YOH directly applied in LRN partially antagonized NRM-evoked inhibition. In a second series of experiments, microinjection cannulas were placed within NRM and LRN in order to determine the effect of blocking alpha 2-receptor activity within LRN on NRM stimulation-produced analgesia in an intact animal. Administration of D,L-homocysteic acid in NRM resulted in a significant increase in baseline tail-flick latency of approximately 140%. Pretreatment with YOH (3 micrograms in 0.5 microliter) in LRN resulted in a significant potentiation of this analgesic effect.(ABSTRACT TRUNCATED AT 400 WORDS)
Murphy
Anne Z
AZ
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267 USA.
Behbehani
Michael M
MM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D005971:Glutamates / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D005971:Glutamates; D006710:Homocysteine; C007956:homocysteic acid; D015016:Yohimbine; D009638:Norepinephrine