A simple method for local delivery of various substances to the rat neuromuscular system

We report here a simple method for the local delivery of various substances to the neuromuscular system in developing and adult rats. This method permits continuous treatment of tissues with a compound over a period of days. Alternative drug delivery systems are unsuitable in neonates. Osmotic pumps are too large and repetitive injections damage the tissues in neonatal rats. Our delivery system provides an adaptable means by which we can directly apply substances in various concentrations in implants of differing sizes. Substances are incorporated into flexible, non-toxic silicone rubber. Strips are cut from the rubber for implantation alongside the muscle or nerve in the anaesthetised animal. The size of the strip is tailored to the length of the muscle or nerve requiring the treatment. Release of the substance from the implant occurs over a period of days and if a longer period of treatment is required, the initial strip can be replaced with a second and even a third implant. We have tested the effects of the substances applied in this manner both physiologically, by examination of muscle function, and morphologically, by muscle histology and retrograde labelling of motoneurones. We have successfully used this method for the application of various groups of substances, including neurotoxins, channel blockers (K+, Ca2+ and Cl-), calcium-chelating agents, protease inhibitors and ionic salts.