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 group in the brain. Although previous studies have examined changes in electrophysiologic activity of LC neurons produced by antidepressant drugs, only a small number have examined changes that occur with chronic drug administration, which is the therapeutically effective regimen, and only one group of investigators has assessed effects on activated (or “burst”) firing of LC neurons under such treatment conditions. The present study assessed changes produced in rats by effective antidepressant treatments—several drugs given chronically (two tricyclic antidepressants, two selective serotonin reuptake 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 also 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 each administration. Electrophysiologic recording of LC activity took place under halothane anesthesia on the last day of drug treatment or following a delay of 1 or 5 days after the final ECS. Results: A common effect of all drugs tested and ECS treatment was to decrease 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 findings reported here are consistent with recent indications that LC neurons are hyperactive in depressed individuals and with suggestions that some behavioral changes seen in depression can arise from consequences of rapidly depolarizing LC terminals, such as release of peptides.