Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity

Background: The locus coeruleus (LC) is the major noradrenergic cell body g roup in the brain. Although previous studies have examined changes in elect rophysiologic activity of LC neurons produced by antidepressant drugs, only a small number have examined changes that occur with chronic drug administ ration, which is the therapeutically effective regimen, and only one group of investigators has assessed effects on activated (or "burst") firing of L C neurons under such treatment conditions. The present study assessed chang es produced in rats by effective antidepressant treatments-several drugs gi ven chronically (two tricyclic antidepressants, two selective serotonin reu ptake inhibitors, and a monoamine oxidase inhibitor) as well as a series of electroconvulsive shocks (ECSs)-in single-unit electrophysiologic activity of LC neurons, measuring effects on spontaneous depolarization rate and al so on sensory-evoked burst firing. Methods: Drugs were administered via osmotic minipumps for either 14 or 30 days; ECSs were administered five times, with a 72-hour interval between ea ch administration. Electrophysiologic recording of LC activity took place u nder halothane anesthesia on the last day of drug treatment or following a delay of I or 5 days after the final ECS. Results: A common effect of all drugs tested and ECS treatment was to decre ase LC spontaneous and sensory-evoked burst firing, Conclusions: The clinical efficacy of antidepressant medication and ECS may be mediated, in part, through reduction of LC neural activity. The finding s reported here are consistent with recent indications that LC neurons are hyperactive in depressed individuals and with suggestions that some behavio ral changes seen in depression can arise from consequences of rapidly depol arizing LC terminals, such as release of peptides. (C) 2001 Society of Biol ogical Psychiatry.