PHARMACOLOGICAL RESPONSES TO PENTOBARBITAL IN DIFFERENT STRAINS OF MICE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 216  (1) , 198-204
Abstract
This study was designed to assess the strain differences in pentobarbital toxicity, narcosis, the development of tolerance and physical dependence, the half-life of pentobarbital and the activities of hepatic microsomal electron transfer chain in DBA/2J, C57BL/6J and ICR mice. The comparisons of responses to acute pentobarbital-induced narcosis with 2 different doses revealed that DBA was most sensitive among the strains. When continuous administration of pentobarbital by pentobarbital pellet implantation is concerned, 4 criteria were used to assess strain differences: determination of the duration of the loss of righting reflex during pentobarbital pellet implantation; cumulative mortality after pentobarbital pellet implantation; degree of tolerance development after 3 days of s.c. implantation of a 75 mg pentobarbital pellet by the relative decrease in the pentobarbital sleeping time and assessment of hyperexcitability by pentylenetetrazol- and audiogenic-induced seizures after pellet removal. The order of susceptibility to continuous pentobarbital pellet implantation was DBA/2J > C57BL/6J > ICR. The biochemical data revealed that the half-life of pentobarbital in DBA/2J mice was significantly longer than that of C57BL/6J or ICR mice in both brain and serum. DBA/2J mice have lower hepatic cytochrome P-450 and cytochrome b5 levels and NADPH dehydrogenase and NADPH-cytochrome c reductase activities as compared with the other strains of mice. The parameters were markedly induced in DBA/2J mice after the development of tolerance to pentobarbital. The differences in genetic variation could be of importance for studies of the barbiturate tolerance mechanism.

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