Electrophysiological effects of Mu-selective opioids on hilar neurons in the hippocampus in vivo.
Although mu-selective opioids have been shown to produce dramatic effects on neurons within the CA1 and dentate regions of the rat hippocampus, little is known regarding their effects on neurons within the hilus, a region of potential importance in several disease states. We studied the neurophysiologic responses of hilar neurons recorded extracellularly to electrophoretic [D-Ala2, NMe-Phe4, Gly-ol]-enkephalin (DAMGO) and systemic morphine (MS) in anesthetized rats. We found that hilar cells could be readily divided into two categories, based on their pattern of spontaneous activity and response to perforant path stimulation. Cells that discharged in a bursting-type pattern formed a homogeneous group electrophysiologically. The response of these cells to opioids was dependent on route of administration, with the spontaneous activity of all cells tested increasing following electrophoretically administered DAMGO, and remaining unchanged in response to systemic MS. Cells that discharged in a non-bursting pattern showed some electrophysiologic variation, as well as some differential response to opioids. However, the spontaneous activity in the majority of non-bursting cells increased following electrophoretic administration of DAMGO. In these cells, MS produced similar, although usually less dramatic, effects. Comparison with intracellular data suggests that the bursting cells in our study correlate most closely with hilar "mossy cells," while the non-bursting action potentials were recorded from other cells, primarily putative interneurons. We conclude that mu-selective opioids produce excitation of mossy cells, probably through an indirect mechanism, with the primary site of action occurring on cells in the granule cell layer. This regional excitation may help to mediate the effects of locally administered mu-selective opioids within the dentate gyrus.
Mayer
J H
JH
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Henriksen
S J
SJ
D000200:Action Potentials / Q000187:drug effects; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects*
D000701:Analgesics, Opioid; D004745:Enkephalins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D009020:Morphine