title: Multiple effects of long-term morphine treatment on postsynaptic beta-adrenergic receptor function in hippocampus: an intracellular analysis.
abstract: We previously reported that beta-adrenergic receptors are increased in cerebral cortex and hippocampus in rats treated chronically with morphine and subsequently down-regulated after morphine withdrawal [22,23]. The changes in receptor density in hippocampus were accompanied by a corresponding super- and subsensitivity, respectively, in beta-adrenergic responsiveness, as assessed electrophysiologically by measuring the ability of isoproterenol to augment population spike responses in the slice. In this study, we compared the ability of isoproterenol to reduce the Ca(2+)-activated K+ slow afterhyperpolarization (slow AHP) in pyramidal neurons in hippocampal slices from opiate-naive and chronic morphine-treated rats to determine whether such changes in beta-adrenergic receptor function are localized postsynaptically. Chronic treatment of rats with morphine produced a 3.5-fold parallel shift to the left in the concentration-response curve for isoproterenol and reduced the EC50 from 4.8 +/- 1.3 to 1.4 +/- 0.5 nM. In contrast, sensitivity and maximal responsiveness to isoproterenol was markedly decreased in pyramidal neurons recorded in slices from morphine withdrawn animals. The concentration-response curves for inhibition of the slow AHP by carbachol or forskolin were not affected by chronic morphine treatment. However, blockade of the slow AHP by forskolin was significantly reduced in pyramidal neurons studied after morphine withdrawal. These data suggest that the increase in electrophysiological responsiveness to beta-adrenergic receptor stimulation found in hippocampus after chronic morphine treatment most likely resulted from an up-regulation in postsynaptic membrane receptors, whereas alterations occurring beyond the receptor level may be involved in the desensitization that is associated with morphine withdrawal.
authors: Department of Physiology, University of Michigan, Ann Arbor 48109-0622.
authors: J M
authors: JM
authors: Ackerman
authors: M D
authors: MD
authors: Womble
authors: H C
authors: HC
authors: Moises
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009020:Morphine / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011943:Receptors, Adrenergic, beta; D009020:Morphine; D002217:Carbachol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D011188:Potassium