Desipramine-induced increase in efflux of endogenous dopamine from rat hypothalamus in vitro: Mechanism and specificity

Abstract

In ritro exposure of minced rat hypothalamus to desipramine (DMI) resulted in a significant elevation of the net efflux of endogenous norepinephrine (NE) and dopamine (DA) at a drug concentration as low as 10 nM. The net efflux of epinephrine was increased only by a 1000-fold greater concentration of desipramine. The increase in efflux of DA was not secondary to changes in the efflux of NE. since nisoxetine elevated the efflux of NE but not of DA and the removal of calcium from the incubation medium blocked the effect of desipramine on the efflux of DA but not of NE. Elimination of calcium did not alter the “spontaneous” hypothalamic efflux of catecholamine. In contrast, desipramine did not affect the net efflux of either DA or NE from the olfactory tubercle or striatum at concentrations of less than 100 μm. At this concentration, the efflux of DA was significantly increased only in the striatum, while the efflux of NE was reduced in the striatum but increased in the olfactory tubercle. Again, in contrast to the hypothalmus, the removal of calcium from the medium markedly reduced “spontaneous” efflux of catecholamine and the desipramine induced efflux of NE. but not the increase in striatal DA efflux produced by desipramine. The results indicate that marked regional differences exist in brain in the ability of desipramine or calcium removal to alter the efflux of both endogenous DA and NE. and suggest that hypothalamic DA and NE neurons are uniquely sensitive to the effects of desipramine.