| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
This research has been performed to extend our previous work, in which the antidepressants desipramine (DMI) and maprotiline (MPL) were shown to induce axonal regeneration of noradrenergic neurons in the rat cerebral cortex. The antidepressants DMI and MPL are known to block the reuptake of noradrenaline (NA), while there are other antidepressants that reveal weak or no potency for NA reuptake blockade. First, to see if antidepressants other than DMI and MPL induce the regeneration of noradrenergic axons, I examined mianserin (MIA) and fluoxetine (FLU). MIA has little or no effect on NA reuptake blockade but may enhance NA release by blockade of presynaptic alpha2-adrenoceptors. FLU is a potent reuptake blocker of serotonin but not of NA. It was found that MIA induced regeneration of cortical noradrenergic axons whereas FLU was ineffective. These findings suggest that the antidepressant-induced regeneration of noradrenergic axons is associated, at least in part, with enhanced noradrenergic transmission.
To see if beta-adrenoceptors are involved in the antidepressant-induced regeneration of noradrenergic axons, the effects of the beta-adrenoceptor blocker propranolol (PRP) was examined. First, the symmetrical sites of the cerebral cortex in the two hemispheres were pretreated with 6-hydroxydopamine (6-OHDA). Two weeks after 6-OHDA pretreatment, the same cortical site of one hemisphere was infused with DMI by means of osmotic minipumps, while the corresponding site of the other hemisphere was infused with DMI (1 mM) + PRP (1 mM). After more than two weeks from start of the infusion, the brain was processed for the immunohistochemistry using an antibody to dopamine-beta-hydroxylase. It was found that PRP attenuated the effects of the DMI-induced regeneration of noradrenergic axons. This finding suggests that beta-adrenoceptors are involved, at least in part, in the antidepressant-induced regeneration of noradrenergic axons.
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