Comparison of the effects of botulinum toxin in adult and neonatal rats: neuromuscular blockade and toxicity

Abstract

A single dose of botulinum toxin (BoTX) was injected subcutaneously to induce neuromuscular blockade in the triceps surae muscles of the hindlimbs of neonatal and adult rats. The efficacy of the toxin in producing complete neuromuscular blockade of the lower limb muscles, assessed by blockade of (a) postural and flexor reflexes and (b) muscle contraction in response to nerve stimulation, was dose dependent at all ages over a BoTX dose range of 10–60 ng/kg. However, BoTX was dramatically more toxic in adult animals resulting in a decline in body weight and lethal consequences in 25% of adult animals 1 week after administration of BoTX doses as low as 40 ng/kg. In contrast, neonatal animals, given the same dosage, continued to grow and no mortalities were observed. The differences in toxicity of BoTX in adult and neonatal rats are readily accounted for by the short duration of effect in the younger animals, which, in turn, is probably the result of more rapid generation of new and functional nerve terminals.Key words: sprouting, toxin botulinism, botulinum toxin, neuromuscular blockade, neonatal muscle.