title: Effects of chronic morphine administration on the mu and delta opioid responses in the CA1 region of the rat hippocampus.
abstract: Extracellular recording of population spike amplitudes in the hippocampal CA1 region were compared in slices from control and chronically morphine-treated rats. Morphine treatment resulted in a decrease in the maximal excitation produced by both mu and delta selective agonists, [N-MePhe3,D-Pro4]-morphiceptin and [D-Pen2,L-Pen5]-enkephalin. The opioid antagonist naloxone did not produce apparent signs of withdrawal in hippocampal slices from morphine-treated rats as shown by a lack of change in the evoked population spike in the presence of 500 nM naloxone. Brain slices from morphine-treated rats that were maintained in the absence of morphine showed signs of tolerance reversal when monitored over an 8-hr period after dissection. If morphine-tolerant slices were maintained in vitro in the presence of 5 microM morphine (the concentration found by high-performance liquid chromatography to be present in the cerebrospinal fluid of morphine-treated rats), there was no significant reversal of tolerance. Furchgott analysis of the [N-MePhe3,D-Pro4]-morphiceptin concentration-response curve shifts induced by the irreversible opioid receptor antagonist beta-chlornaltrexamine revealed an apparent 50% spare receptor reserve for the mu selective agonist in slices from drug-naive rats. beta-Chlornaltrexamine (20 nM) treatment and chronic morphine exposure resulted in a similar reduction in the maximal response to [N-MePhe3,D-Pro4]morphiceptin. This observation indicates that the development of morphine tolerance resulted in an elimination of the spare opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle.
authors.forename: T L
authors.initials: TL
authors.lastname: Wimpey
authors.forename: K E
authors.initials: KE
authors.lastname: Opheim
authors.forename: C
authors.initials: C
authors.lastname: Chavkin
mesh_terms: D000818:Animals; D004361:Drug Tolerance; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
chemical_list: D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C017120:chlornaltrexamine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-