Effects of indolic neurotoxins on enteric serotonergic neurons

The effects of the indolic neurotoxins 5,6- and 5,7-dihydroxytryptamine (5,6-DHT; 5,7-DHT) on the enteric nervous system were examined. 5,6-DHT, in moderate dosage, 40 mg/kg, decreased uptake of tritiated 5-hydroxytryptamine (3H-5-HT) but not that of tritiated norepinephrine (3H-NE). However, selectivity of the neurotoxins for enteric serotonergic rather than adrenergic axons was enhanced by pretreating animals with desmethylimipramine to inhibit the catecholamine uptake mechanism. When this was done, 5,7-DHT was found to prevent the development of 5-HT histofluorescence (following injection of L-tryptophan) without affecting histofluorescence of NE. In contrast, 6-hydroxydopamine virtually abolished NE histofluorescence and uptake of 3H-NE without affecting development of 5-HT histofluorescence or uptake of 3H-5-HT. Electron microscopy revealed that b,7-DHT induced dose-dependent lesions of axonal varicosities in the enteric nervous system. Early lesions, 1--4 hours following injection, resembled cytolysosomes and consisted of membrane enclosed regions of opaque cytoplasm containing synaptic vesicles. Affected varicosities contained a mixed population of large dense cored (approximately 120 nm) and small lucent vesicles (approximately 70 nm) but none exhibited pre- or postsynaptic membrane specializations. After 24 hours terminals degenerated and were engulfed by surrounding supporting cells. It is concluded that peripheral serotonergic neurons resemble central serotonergic neurons in susceptibility to the toxic effects of indolic neurotoxins. These neurotoxins are useful anatomical markers of serotonergic terminal varicosities.