EFFECTS OF ETHANOL ON DEVELOPMENT OF DORSAL RAPHE TRANSPLANTS INOCULO - A MORPHOLOGICAL AND ELECTROPHYSIOLOGICAL STUDY

The purpose of this project was to investigate ethanol influence on the development of serotonin-containing (5-HT) neurons of the dorsal raphe nucleus in rat. Fetal tissue of embryonic day 17 from the dorsal brainstem was grafted to the anterior chamber of the eye of adult albino rats. The experimental group was exposed to 16% ethanol in the drinking water, and the control group received water ad libitum. After 4 weeks, morphological and electrophysiological evaluations were performed. Immunohistochemical analysis showed that 5-HT-immunoreactive fibers from ethanol-treated transplants had a disturbed outgrowth pattern into the host iris as compared to the control group. Furthermore, the outgrowth area and axon bundle formation was significantly greater in the control group than in the ethanol group. Electrophysiological recordings revealed a dose-dependent biphasic effect of locally applied ethanol on transplanted monoaminergic neurons. Low doses of ethanol (0.5-3 mM) induced an increase in basal firing rate of control neurons, while higher doses (10-100 mM) caused inhibition. However, monoaminergic neurons in the ethanol group showed a decreased neuronal sensitivity to locally applied ethanol. The same dose of locally applied ethanol which produced an excitation of neuronal activity in the ethanol transplants produced an inhibition in the control grafts. The dose-response curve was shifted to the right. The present results suggest that chronic ethanol exposure during early development leads to altered axonal outgrowth from brainstem 5-HT neurons, as well as decreased sensitivity of these neurons to locally applied ethanol.