Abstract
Ammonia and benzodiazepines are thought to be involved in the pathogenesis of hepatic encephalopathy. The present study was undertaken to evaluate the effect of various benzodiazepine-receptor ligands and neurosteroids on ammonia toxicity in mice. Administration of ammonium acetate (8-15 mmole/kg; i.p.) to Swiss Webster mice resulted in a dose-dependent increase in mortality. Pretreatment with the central benzodiazepine receptor agonist clonazepam or the antagonist Ro15-1788 (7 mg/kg each; i.p.) had no significant effect on the lethal response to 10 mmole/kg ammonium acetate. However, pretreatment with the putative antagonist of the peripheral-type benzodiazepine receptor, PK 11195 (10 mg/kg; i.p.), reduced mortality from 50 to 10%. Ro5-4864 (10 mg/kg; i.p.), an agonist of the peripheral-type benzodiazepine receptors, had no effect on ammonia toxicity. The neurosteroid, pregnenolone sulfate (20 mg/kg; i.p.) reduced mortality from 50 to 25%. The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (2 mg/kg; i.p.), had no effect on the lethal response to ammonium acetate. The results from the present study suggest a role for peripheral-type benzodiazepine receptors and specific neurosteroids in the alleviation of ammonia toxicity in mice.
| Original language | English |
|---|---|
| Pages (from-to) | 251-254 |
| Number of pages | 4 |
| Journal | Neuroscience Letters |
| Volume | 182 |
| Issue number | 2 |
| DOIs | |
| State | Published - Dec 5 1994 |
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Keywords
- Ammonia
- Central-type benzodiazepine receptor
- Hepatic encephalopathy
- Neurosteroid
- Peripheral-type benzodiazepine receptor
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Attenuation of ammonia toxicity in mice by PK 11195 and pregnenolone sulfate. / Itzhak, Yossef; Norenberg, Michael D.
In: Neuroscience Letters, Vol. 182, No. 2, 05.12.1994, p. 251-254.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Attenuation of ammonia toxicity in mice by PK 11195 and pregnenolone sulfate
AU - Itzhak, Yossef
AU - Norenberg, Michael D
PY - 1994/12/5
Y1 - 1994/12/5
N2 - Ammonia and benzodiazepines are thought to be involved in the pathogenesis of hepatic encephalopathy. The present study was undertaken to evaluate the effect of various benzodiazepine-receptor ligands and neurosteroids on ammonia toxicity in mice. Administration of ammonium acetate (8-15 mmole/kg; i.p.) to Swiss Webster mice resulted in a dose-dependent increase in mortality. Pretreatment with the central benzodiazepine receptor agonist clonazepam or the antagonist Ro15-1788 (7 mg/kg each; i.p.) had no significant effect on the lethal response to 10 mmole/kg ammonium acetate. However, pretreatment with the putative antagonist of the peripheral-type benzodiazepine receptor, PK 11195 (10 mg/kg; i.p.), reduced mortality from 50 to 10%. Ro5-4864 (10 mg/kg; i.p.), an agonist of the peripheral-type benzodiazepine receptors, had no effect on ammonia toxicity. The neurosteroid, pregnenolone sulfate (20 mg/kg; i.p.) reduced mortality from 50 to 25%. The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (2 mg/kg; i.p.), had no effect on the lethal response to ammonium acetate. The results from the present study suggest a role for peripheral-type benzodiazepine receptors and specific neurosteroids in the alleviation of ammonia toxicity in mice.
AB - Ammonia and benzodiazepines are thought to be involved in the pathogenesis of hepatic encephalopathy. The present study was undertaken to evaluate the effect of various benzodiazepine-receptor ligands and neurosteroids on ammonia toxicity in mice. Administration of ammonium acetate (8-15 mmole/kg; i.p.) to Swiss Webster mice resulted in a dose-dependent increase in mortality. Pretreatment with the central benzodiazepine receptor agonist clonazepam or the antagonist Ro15-1788 (7 mg/kg each; i.p.) had no significant effect on the lethal response to 10 mmole/kg ammonium acetate. However, pretreatment with the putative antagonist of the peripheral-type benzodiazepine receptor, PK 11195 (10 mg/kg; i.p.), reduced mortality from 50 to 10%. Ro5-4864 (10 mg/kg; i.p.), an agonist of the peripheral-type benzodiazepine receptors, had no effect on ammonia toxicity. The neurosteroid, pregnenolone sulfate (20 mg/kg; i.p.) reduced mortality from 50 to 25%. The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (2 mg/kg; i.p.), had no effect on the lethal response to ammonium acetate. The results from the present study suggest a role for peripheral-type benzodiazepine receptors and specific neurosteroids in the alleviation of ammonia toxicity in mice.
KW - Ammonia
KW - Central-type benzodiazepine receptor
KW - Hepatic encephalopathy
KW - Neurosteroid
KW - Peripheral-type benzodiazepine receptor
UR - http://www.scopus.com/inward/record.url?scp=0027962338&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027962338&partnerID=8YFLogxK
U2 - 10.1016/0304-3940(94)90809-5
DO - 10.1016/0304-3940(94)90809-5
M3 - Article
C2 - 7715821
AN - SCOPUS:0027962338
VL - 182
SP - 251
EP - 254
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -