Possible relationship of the locus coeruleus--hippocampal noradrenergic neurons to depression and mode of action of antidepressant drugs.

Recent studies performed in our laboratory suggest involvement of locus coeruleus (LC) and hippocampal noradrenergic (NE) neurons in the mechanism of depression and mode of action of antidepressants. Both electrolytic and 6-OHDA lesions to the LC abolished desipramine action in forced swim test in rats. The action of desipramine was also reduced in rats pretreated with alpha 1 adrenolytic drugs -- phenoxybenzamine and prazosin. Electrical stimulation of the LC produced, like desipramine, activating effect in forced swim test, the phenomenon never observed in phenoxybenzamine-pretreated animals. Chronic (but not acute) administration of desipramine potentiated activatory effects of intrahippocampal injections of NE and phenylephrine but not isoprenaline in both open field and forced swim test. Depressant effect of intrahippocampal clonidine was reversed by chronic desipramine (in the open field test). The effect of desipramine was partially shared by citalopram.