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J Neurophysiol 87: 2464-2470, 2002;
0022-3077/02 $5.00
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The Journal of Neurophysiology Vol. 87 No. 5 May 2002, pp. 2464-2470
Copyright ©2002 by the American Physiological Society

Chronic Morphine Treatment Alters Endogenous Opioid Control of Hippocampal Mossy Fiber Synaptic Transmission

John M. Harrison,1 Richard G. Allen,2 Michael J. Pellegrino,2 John T. Williams,1 and Olivier J. Manzoni1,3

 1Vollum Institute and  2Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland, Oregon 97201; and  3Actions Concertéés Initiatives Jeunes Chercheurs "Plasticité Synaptique et Toxicomanie," Centre National de la Recherche Scientifique Unité Propre de Recherche 9023, 34094 Montpellier Cedex 05, France

Harrison, John M., Richard G. Allen, Michael J. Pellegrino, John T. Williams, and Olivier J. Manzoni. Chronic Morphine Treatment Alters Endogenous Opioid Control of Hippocampal Mossy Fiber Synaptic Transmission. J. Neurophysiol. 87: 2464-2470, 2002. Synaptic adaptations are thought to be an important component of the consequences of drug abuse. One such adaptation is an up-regulation of adenylyl cyclase that has been shown to increase transmitter release at several inhibitory synapses. In this study the effects of chronic morphine treatment were studied on mossy fiber synapses in the guinea pig hippocampus using extracellular field potential recordings. This opioid-sensitive synapse was chosen because of the known role of the adenylyl cyclase cascade in the regulation of glutamate release. Long-term potentiation (LTP) at the mossy fiber synapse was enhanced after chronic morphine treatment. In control animals, opioid antagonists increased LTP but had no effect in morphine-treated guinea pigs. In contrast, the long-lasting depression of transmission induced by a mGluR agonist and CA1 LTP were not altered. Chronic morphine treatment neither caused tolerance to µ- and kappa -receptor-mediated inhibition at the mossy fiber synapse nor modified total hippocampal dynorphin levels. The results suggest that the phasic inhibition of glutamate transmission mediated by endogenous opioids is reduced after chronic exposure to morphine.




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