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-systemic encephalopathy, but its relevance to human portal-systemic encephalopathy remains uncertain. Specifically, it has not been demonstrated that the behavioral changes seen in this model respond to measures known to improve portal-systemic encephalopathy in human subjects. Accordingly, the aim of this study was to establish whether neomycin (an effective treatment for portal-systemic encephalopathy in human beings) added to the drinking water of rats subjected to portacaval shunt reversed or ameliorated the reduction in spontaneous motor activity, which represents a measure of encephalopathy in this animal model. A randomized, placebo-controlled crossover design was used, with each animal serving 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; this was followed by 1 wk off neomycin; in group B rats, the sequence was reversed. Spontaneous intake of neomycin for 7 days at doses comparable to human usage (0.1 to 0.2 gm/kg/day) was associated with a significant increase in spontaneous motor activity in rats subjected to portacaval shunt (26.4% in group A, 66.3% in group B; p < 0.01 for each protocol) with no significant effect in sham-operated animals. Withdrawal of neomycin resulted in reversal of this effect in group A rats subjected to portacaval shunt. Similar significant improvements for exploratory activity as measured on the basis of nose-hole pokes was also seen in rats subjected to portacaval shunt and given neomycin.(ABSTRACT TRUNCATED AT 250 WORDS)
Conjeevaram
H S
HS
Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio 44109-1998.
Nagle
A
A
Katz
A
A
Kaminsky-Russ
K
K
McCullough
A J
AJ
Mullen
K D
KD
D000641:Ammonia / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009355:Neomycin / Q000627:therapeutic use*; D011167:Portacaval Shunt, Surgical / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000641:Ammonia; D009355:Neomycin