Journal of Neuroscience, Vol 10, 3793-3800, Copyright © 1990 by Society for Neuroscience
Dynorphin A-(1-17) induces alterations in free fatty acids, excitatory amino acids, and motor function through an opiate-receptor-mediated mechanism
R Bakshi, AH Newman and AI Faden
Department of Neurology, University of California, San Francisco 94121.
The endogenous opioid dynorphin A-(1-17) (Dyn A) has been implicated as a
mediator of tissue damage after traumatic spinal cord injury (TSCI) and
causes hindlimb paralysis when administered intrathecally. Motor impairment
following intrathecal Dyn A is attenuated by antagonists of excitatory
amino acids (EAAs); whether opioid receptors mediate such injury has been
questioned. TSCI causes various biochemical changes associated with
secondary tissue damage, including alterations in tissue amio acids,
phospholipids, and fatty acids. Such changes reflect injury severity and
correlate with motor dysfunction. The present studies examined whether
dynorphin administration causes similar biochemical alterations and whether
effects of Dyn A can be modified by treatment with opioid-receptor
antagonists. At 24 hr after intrathecal Dyn A, there were significant
declines in tissue levels of glutamate, aspartate, and glycine. Increases
in total free fatty acids were found at 2 and 24 hr, reflecting changes in
both saturated and unsaturated components, which were associated with
significant decreases in tissue cholesterol and phospholipid phosphorus at
the earlier time point. Each of these neurochemical changes, as well as
corresponding motor deficits, were limited by pretreatment with the opioid
antagonist nalmefene. In separate experiments, both nalmefene and the
selective kappa-opioid antagonist nor-binaltorphimine (nor-BNI) limited
dynorphin- induced motor dysfunction; effects of nor-BNI were dose related,
and those of nalmefene were stereospecific. Therefore, behavioral and
neurochemical consequences of Dyn A administration are mediated in part
through opiate receptors, most likely kappa-receptors.(ABSTRACT TRUNCATED
AT 250 WORDS)