Modulation of noradrenergic neuronal firing by selective serotonin reuptake blockers

Using in vivo extracellular unitary recording, the effect of short term (2- day) and long-term (21-day) administration of the selective 5-HT reuptake i nhibitor (SSRI) paroxetine (10 mg kg(-1) day(-1), s.c. using osmotic minipu mps) was examined on the spontaneous tiring activity of locus coeruleus nor adrenergic neurons. Long-term but not short-term treatment significantly de creased firing activity. Thus, it appears that enhancing 5-HT neurotransmis sion by sustained SSRI administration leads to a reduction of the firing ra te of noradrenergic neurons. The SSRI paroxetine therefore alters the activ ity of noradrenergic neurons with a delay that is consistent with its thera peutic action in depression and panic disorder.