Effects of tetrodotoxin on naloxone-precipitated withdrawal syndrome in morphine-dependent rats and mice

The protective and therapeutic effects of tetrodotoxin (TTX, rats, 0.003-0.1 μg·kg -1 , im, for 5 d; mice, 0.02-0.2 μg·kg -1 ·d -1 , ip, for 2 d) on withdrawal syndrome induced by naloxone (Nal)were investigated in morphine dependent rats and mice. The results showed that the loss of body weight of rats was significantly inhibited (P0.01) by TTX. The jumping responses precipitated by Nal in mice were inhibited significantly by TTX administered 2 d before the challenge with Nal. TTX significantly inhibited the withdrawal syndrome evoked by Nal in morphine dependent rats and mice, and its effects were similar to that of clonidine. In the range of dose used in this study, TTX did not affect the blood pressure, respiration and heart rate, and did not affect the nicotine induced neural reflex responses in anesthetized rats. TTX had no effects on ethanoic acid writhing response and spontaneous movements of the mice.