REVERSAL OF BEHAVIORAL-CHANGES IN RATS SUBJECTED TO PORTACAVAL-SHUNT WITH ORAL NEOMYCIN THERAPY

The portacaval shunt rat is often used as a model of human portal-syst emic encephalopathy, but its relevance to human portal-systemic enceph alopathy remains uncertain. Specifically, it has not been demonstrated that the behavioral changes seen in this model respond to measures kn own to improve portal-systemic encephalopathy in human subjects. Accor dingly, the aim of this study was to establish whether neomycin (an ef fective treatment for portal-systemic encephalopathy in human beings) added to the drinking water of rats subjected to portacaval shunt reve rsed or ameliorated the reduction in spontaneous motor activity, which represents a measure of encephalopathy in this animal model. A random ized, placebo-controlled crossover design was used, with each animal s erving as its own control. After establishment of baseline activities, 12 rats with portacaval shunt and 12 sham-operated rats were divided into two equal groups: Group A animals received neomycin for 1 wk; thi s was followed by 1 wk off neomycin; in group B rats, the sequence was reversed. Spontaneous intake of neomycin for 7 days at doses comparab le to human usage (0.1 to 0.2 gm/kg/day) was associated with a signifi cant increase in spontaneous motor activity in rats subjected to porta caval shunt (26.4% in group A, 66.3% in group B; p < 0.01 for each pro tocol) with no significant effect in sham operated animals. Withdrawal of neomycin resulted in reversal of this effect in group A rats subje cted to portacaval shunt. Similar significant improvements for explora tory activity as measured on the basis of nose-hole pokes was also see n in rats subjected to portacaval shunt and given neomycin. These neom ycin-associated changes in the motor activity of rats subjected to por tacaval shunt could not be attributed to any effect of neomycin on ser um ammonia level. These findings support the concept that the rat subj ected to portacaval shunt is a valid model of human portal-systemic en cephalopathy that can be used to explore the pathophysiology of this s yndrome.