EXACERBATION OF CARBON TETRACHLORIDE-INDUCED LIVER-INJURY IN THE RAT BY METHAMPHETAMINE

The effect of methamphetamine cotreatment on carbon tetrachloride-induced liver toxicity was examined in male Sprague-Dawley rats. Concurrent administration of methamphetamine was found to greatly increase the extent of liver injury resulting from carbon tetrachloride treatment, as indicated both by measurement of serum alanine aminotransferase (ALT) activity and from direct histopathologic examination. Concurrent administration of methamphetamine doses less than 10 mg/kg (i.p.), or administration of methamphetamine either before (-3 h) or after (3-9 h) the carbon tetrachloride dose, did not significantly increase liver injury from carbon tetrachloride. These observations indicate that the potentiation by methamphetamine of carbon tetrachloride hepatoxicity previously observed in the mouse also occurs in the rat, and that the timing of the methamphetamine and carbon tetrachloride doses is critical for the interaction.