Dermorphin-induced hyperexcitability in hippocampal CA3 and CA1 in vitro.
Dermorphin, a specific mu 1-opioid receptor agonist, has been studied for its effects on the physiology of the rat hippocampal slice. Population responses in CA3 to threshold levels of stimulation from both the Schaffer collaterals and mossy fibers were markedly enhanced in the presence of 50-100 nM dermorphin, while CA1 responses to threshold Schaffer collateral stimulation were less effected. Responses at higher stimulus levels than threshold were negligibly responsive to dermorphin, although at 500 nM dermorphin all responses became epileptiform and in some slices spontaneous bursting erupted. [L-Ala2]Dermorphin, a biologically inactive dermorphin analogue, did not increase response amplitudes nor evoke epilepsy in the slice. 5 microM naloxone blocked the effect of dermorphin on Schaffer collateral and mossy fiber-evoked responses, though less effectively in the latter case. These data provide in vitro evidence to support in vivo observations that excessive mu-opioid receptor activation can be proconvulsant in the hippocampus, but that normally the receptors may function as facilitatory modulators of responses in the threshold range.
Jones
L S
LS
Department of Developmental Biology and Anatomy, University of South Carolina School of Medicine, Columbia 29208.
Grooms
S Y
SY
Salvadori
S
S
Lazarus
L H
LH
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists*
D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C030058:dermorphin; D009270:Naloxone