EFFECTS OF ACUTE, CHRONIC ETHANOL AND WITHDRAWAL ON DORSAL RAPHE NEURONS - ELECTROPHYSIOLOGICAL STUDIES

The effect of a single intravenous administration of ethanol (0.25-1.0 g/kg) on the spontaneous activity of putative serotonin neurons of th e dorsal raphe nucleus was studied in unanesthetized rats. Ethanol pro duced a slight but progressive decline in neuronal activity in 67% (si x of nine) of all neurons tested. The remaining 33% (three of nine) we re unresponsive. Upon withdrawal of chronic ethanol treatment (1-5 g/k g every 6 h for six consecutive days, 12 h from last ethanol administr ation), the mean firing rate of dorsal raphe neurons was found to be s ignificantly reduced, by about 30% (n=71), as compared with the contro l group (n=83), whereas the cells/track index was unaltered. Under the se conditions, ethanol administration further reduced firing rare in 6 7% (four of six) of all the neurons tested. In the remaining 33% (two of six), no response was observed. At 72 h after the last ethanol admi nistration, the mean firing rate of dorsal raphe neurons was found to be within control values (n=90). Further, to evaluate the functional s tatus of the autoreceptors under control conditions and after withdraw al from chronic ethanol, the selective seretonin-1A receptor agonist 8 -hydroxy-(2-di-n-propylamino)tetralin was administered intravenously i n cumulative doses (1-16 mu g/kg) and dose-response curves were genera ted for both groups. Autoreceptor sensitivity of dorsal raphe neurons was found to be not statistically different in control and ethanol wit hdrawn rats (n=6 for both groups) as indexed by a similar potency disp layed by 8-hydroxy-(2-di-n-propylamino)tetralin in reducing the sponta neous activity of dorsal raphe neurons. The results indicate that, in spite of the widespread use of serotonin transmission potentiating age nts in the treatment of alcoholism, neither acute nor withdrawal from chronic ethanol administration produces drastic effects on dorsal raph e neurons. However, the inhibition of dorsal raphe neuronal activity a fter acute ethanol may be due to the reported ability of ethanol to in crease serotonin release from terminal areas. This increased serotonin tone could, at the level of recurrent axon collaterals in the dorsal raphe nucleus, reduce the spontaneous activity of the cells. On the ot her hand, a similar reduction in spontaneous activity after withdrawal from ethanol correlates well with the reduction in serotonin levels o bserved under these conditions in microdialysis studies. (C) 1997 IBRO .