Effects of antidepressants on the uptake and release of norepinephrine from rat cerebral cortex

The effects of several antidepressants on the release of (3H)-norepinephrine (NE) from homogenates of rat cerebral cortex were studied. A continuous superfusion collection system was used in order to differentiate these effects from effects on reuptake. Amitriptyline, maprotiline, mianserin, and trazodone produced a statistically significant decrease in spontaneous tritium efflux when present in the superfusion medium at a concentration of 1.0 microM. The other antidepressants studied had no effect. We used a buffer with the K+ concentration raised to 56 mM as a model of depolarization-induced release. Desipramine, fluoxetine, and iprindole (again at 1.0 microM) caused a significant decrease in this measure. These results indicate that some of both the tricyclic and atypical antidepressants may alter spontaneous or depolarization-induced release of NE.