Loss of inhibition in the spinal cord during barbiturate withdrawal

Three types of inhibition in the spinal cord were studied during barbiturate withdrawal. Cats were made physically dependent on pentobarbital using a standard technique for chronic treatment developed in this laboratory. All animals treated this way developed severe withdrawal signs including spontaneous grand mal type convulsions, upon abrupt drug withdrawal. Animals were prepared for electrophysiological studies 48 hours after the last dose of chronic pentobarbital treatment, near peak intensity of the withdrawal syndrome. Under halothane anesthesia, the neuraxis was sectioned at C1 and both common carotid arteries were ligated. The animal was then respired on room air. The lumbar spinal cord was exposed by laminectomy, a hindleg was dissected to allow stimulation of peripheral nerves and action potentials were recorded from ventral roots L7 and S1 that had been cut near their exits through the dura mater. Recurrent (Renshaw cell-mediated) inhibition was almost totally absent during barbiturate withdrawal. Presynaptic inhibition was also decreased. Postsynaptic inhibition was little affected by barbiturate dependence. These findings indicate that loss of function in inhibitory pathways plays a role in barbiturate dependence and withdrawal.