Retrograde axonal transport following injection of [3H]serotonin in the olfactory bulb. I. Biochemical study.

A retrograde axonal transport from the serotonergic nerve terminals in the olfactory bulb (OB) to their parent cell bodies in the midbrain raphe nuclei has been demonstrated after stereotaxic injection of [2H]5-HT into the OB of rats pretreated with a monoamine oxidase (MAO) inhibitor: at various time intervals thereafter (4-92 h) there was a preferential accumulation of radioactivity mainly in the raphe dorsalis nucleus (RDN). Maximal accumulation occurred at 24 h. Of this radioactivity, 30-50% was recovered as 5-HT. The accumulation was estimated to take place at two rates: a fast one (48 mm/day) and a slower one (16 mm/day). Under the same experimental conditions there was no clear evidence for a retrograde accumulation of [3H]norepinephrine in the RDN. A passive diffusion mechanism could be excluded since the diffuson of tracer towards the cerebrospinal fluid was prevented by prior mechanical obstruction of the olfactory diverticle of the lateral ventricle. Furthermore, colchicine strongly reduced (by 80%) the radioactive accumulatin in the RDN. Destruction of serotonergic nerve terminals by 5,6-dihydroxytryptamine or inhibiton of 5-HT uptake by fluoxetine decreased this retrograde accumulation whereas destruction of catecholaminergic nerve terminals by 6-hydroxydopamine was without effect. Pretreatment with reserpine decreased the amount of radioactivity transported to the RDN by 40%. In the absence of MAO inhibition pretreatment, animals still presentd 35% of the tracer transported to the RDN. Intrabulbar injection of MAO inhibitor did not affect the accumulation rates when compared with animals which received the inhibitor by the intraperitoneal route. In conclusion, the retrograde axonal transport following [3H]5-HT injection in the serotonergic RDN-OB system occurs via an active process which depends on a colchicine-sensitive mechanism and is partially linked to a reserp ine-sensitive structure. During its transport, the amine seems to be relatively protected from metabolic inactivation.