TY - JOUR T1 - Effects of chronic morphine administration on the mu and delta opioid responses in the CA1 region of the rat hippocampus. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 405 LP - 411 VL - 251 IS - 2 AU - T L Wimpey AU - K E Opheim AU - C Chavkin Y1 - 1989/11/01 UR - http://jpet.aspetjournals.org/content/251/2/405.abstract N2 - 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) ER -