Handling-induced convulsions (HIC) as a sensitive index of hyperexcitability associated with the high pressure nervous syndrome (HPNS)

The earliest threshold for the onset of hyperexcitability induced by HPNS in humans is easily determined by the disruption of simple motor tasks. However in rodents, the determination of similar thresholds is much more problematic. Handling-induced convulsions have long been used in mice as an index of hyperexcitability associated with drug withdrawal syndromes (e.g. alcohol), where it has been found to be a sensitive measure. We report here an adaptation of HIC for use in a sealed hyperbaric chamber. Since these convulsions are elicited by lifting the mice by the tail, we developed a prototype apparatus which allows freedom of movement by the animals, yet the animals can be lifted by any desired interval by means of a fully proportional servo (Futaba FP-S48) actuated by a joy stick outside the chamber. A stainless steel braided line is taped to the animal's tail, with the other end connected to an arm on the servo mechanism. Each animal is housed in a narrow (7 x 17 cm), but tall plexiglass enclosure, which allows full view of the three mice run at one time. Handling-induced convulsion scores were elevated by high pressure in heliox at pressures as low as 20 atmospheres, which is well below the thresholds for spontaneous clonic or tonic-clonic convulsions. This technique is especially useful in making direct comparisons between the hyperexcitability states associated with high pressure and those associated with alcohol and other drug withdrawal syndromes, where HIC is the predominant withdrawal sign in the literature with mice.