Mu Opiates Inhibit Long-Term Potentiation Induction in the Spinal Cord Slice

• Published in: Journal of neurophysiology Vol. 85; no. 2; pp. 485 - 494
• Main Authors: Terman, Gregory W, Eastman, Clifford L, Chavkin, Charles
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01-02-2001
• Subjects: Animals; Electric Stimulation; Enkephalin, Ala-MePhe-Gly- - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Ganglia, Spinal - physiology; In Vitro Techniques; Long-Term Potentiation - drug effects; Neural Inhibition - physiology; Presynaptic Terminals - physiology; Rats; Receptors, Opioid, mu - agonists; Spinal Cord - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.2001.85.2.485

  1 Department of Anesthesiology,
  2 Department of Pharmacology, and the Graduate
Program in Neurobiology and Behavior, University of Washington School
of Medicine, Seattle, Washington 98195-6540
Terman, Gregory W.,
Clifford L. Eastman, and
Charles Chavkin.
Mu Opiates Inhibit Long-Term Potentiation Induction in the
Spinal Cord Slice. J. Neurophysiol. 85: 485-494, 2001. Long-term potentiation (LTP) involves a
prolonged increase in neuronal excitability following repeated afferent
input. This phenomenon has been extensively studied in the hippocampus
as a model of learning and memory. Similar long-term increases in neuronal responses have been reported in the dorsal horn of the spinal
cord following intense primary afferent stimulation. In these studies,
we utilized the spinal cord slice preparation to examine effects of the
potently antinociceptive mu opioids in modulating primary
afferent/dorsal horn neurotransmission as well as LTP of such
transmission. Transverse slices were made from the lumbar spinal cord
of 10- to 17-day-old rats, placed in a recording chamber, and perfused
with artificial cerebrospinal fluid also containing bicuculline (10 µM) and strychnine (1 µM). Primary afferent activation was achieved
in the spinal slice by electrical stimulation of the dorsal root (DR)
or the tract of Lissauer (LT) which is known to contain a high
percentage of small diameter fibers likely to transmit nociception.
Consistent with this anatomy, response latencies of LT-evoked field
potentials in the dorsal horn were considerably slower than the
response latencies of DR-evoked potentials. Only LT-evoked field
potentials were found to be reliably inhibited by the mu opioid
receptor agonist [ D -Ala 2 ,
N-Me-Phe 4 , Gly 5 ]
enkephalin-ol (DAMGO, 1 µM), although evoked potentials from both DR
and LT were blocked by the AMPA/kainate glutamate receptor antagonist
6-cyano-7-nitroquinoxalene-2,3-dione. Moreover repeated stimulation of
LT produced LTP of LT- but not DR-evoked potentials. In contrast,
repeated stimulation of DR showed no reliable LTP. LTP of LT-evoked
potentials depended on N -methyl- D -aspartate
(NMDA) receptor activity, in that it was attenuated by the NMDA
antagonist APV. Moreover, such LTP was inhibited by DAMGO interfering
with LTP induction mechanisms. Finally, in whole cell voltage-clamp studies of Lamina I neurons, DAMGO inhibited excitatory postsynaptic current (EPSC) response amplitudes from LT stimulation-evoked excitatory amino acid release but not from glutamate puffed onto the
cell and increased paired-pulse facilitation of EPSCs evoked by LT
stimulation. These studies suggest that mu opioids exert their
inhibitory effects presynaptically, likely through the inhibition of
glutamate release from primary afferent terminals, and thereby inhibit
the induction of LTP in the spinal dorsal horn.