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Journal of Neuroscience, Vol 15, 6939-6945, Copyright © 1995 by Society for Neuroscience
A comparison of the role of dynorphin in the hippocampal mossy fiber pathway in guinea pig and rat
PA Salin, MG Weisskopf and RA Nicoll
Department of Cellular and Molecular Pharmacology, University of California at San Francisco 94143, USA.
Several behavioral studies in rat (Gallagher, 1988) have suggested that
opioids in the hippocampus could play an important role in learning and
memory. However, in this species, very few reports specifically address the
issue of physiological actions of opioids released by the mossy fibers
which constitute the principal source of dynorphin and enkephalin in the
hippocampus. In the guinea pig high frequency stimulation of mossy fibers
causes a transient heterosynaptic inhibition of neighboring mossy fibers
(Weisskopf et al., 1993) or perforant path synapses in the dentate (Wagner
et al., 1993), which is mediated by the synaptic release of dynorphin that
activates presynaptic kappa receptors. We show here that neither exogenous
nor endogenous dynorphin affect mossy fiber excitatory postsynaptic
potentials in the Sprague-Dawley rat, which is consistent with the finding
that kappa receptor binding in the mossy fiber termination zone is dense in
the guinea pig and sparse in this rat. More surprisingly, although kappa
receptor binding is found in the rat dentate gyrus molecular layer and in
the CA3 pyramidal cell layer, dynorphin had no action on perforant path
field responses, somatic potassium currents or evoked monosynaptic
inhibitory postsynaptic currents in CA3 cells. This lack of action appears
to be an exception among rodents as dynorphin significantly inhibited mossy
fiber responses in the hamster, mouse, and even another strain of rat,
Long-Evans. Unlike the kappa mediated actions, the mu opioid receptor
agonist DAMGO inhibited Sprague-Dawley mossy fiber responses, as it does in
guinea pig. In contrast to other investigators, however, we found that the
opioid receptor antagonist naloxone had no effect on Sprague-Dawley mossy
fiber LTP.
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