LOCUS-COERULEUS NEURONS FROM MORPHINE-TREATED RATS DO NOT SHOW OPIATE-WITHDRAWAL HYPERACTIVITY IN-VITRO

In vitro studies have not consistently demonstrated naloxone-precipita ted opiate-withdrawal hyperactivity of locus coeruleus neurons. The re ason for this inconsistency may be because partial or complete withdra wal occurred during preparation of the locus coeruleus slice. The aim of the present study was to assay opiate withdrawal-related hyperactiv ity in neurons recorded from locus coeruleus slices while ensuring the maintenance of dependence until naloxone-precipitated withdrawal. Ext racellular recordings were obtained from individual locus coeruleus ne urons in slices from morphine-treated and drug-naive rats. Morphine 1 mu M was present in all solutions during preparation and recording in slices from morphine-treated rats. The average firing rate of the drug -naive controls was 0.93 Hz (+/- 0.04 Hz). Bath application of morphin e (1 mu M) almost completely suppressed firing in drug-naive controls (0.058 Hz, +/- 0.04 Hz, n = 12), whereas in solutions containing 1 mu M morphine, the firing rate of cells from morphine-treated rats averag ed 0.71 Hz (+/- 0.05 Hz), indicating considerable, but incomplete tole rance. In the same slices, naloxone increased the average spontaneous firing of locus coeruleus cells to 0.96 Hz (+/- 0.04 Hz). Thus, naloxo ne did not produce withdrawal hyperactivity, but returned the cells fr om morphine-treated rats to control rates. We conclude that locus coer uleus cells in locus coeruleus slice preparations from morphine-treate d rats did not demonstrate withdrawal-related hyperactivity even when dependence was maintained until naloxone-precipitated withdrawal. Thus , our results do not support a role for adaptations intrinsic to locus coeruleus neurons in withdrawal hyperexcitability, but instead imply the necessity of functional afferent activity. (C) 1998 Elsevier Scien ce B.V.