Pertussis toxin treatment results in tolerance to the depressant effects of opioid, monoaminergic, and muscarinic agonists on dorsal-horn network responses in mouse spinal cord-ganglion cultures

Abstract

After treatment of mouse spinal cord-ganglion explants with pertussis toxin (PTX), the acute depressant effects of opioids on sensory-evoked dorsal-horn network responses are markedly attenuated, and characteristic cord discharges can then occur even in the presence of greater than 100-fold higher opioid concentrations, as observed after chronic exposure to opioids. The usual acute depressant effects of serotonin, norepinephrine, and oxotremorine on dorsal-horn discharges are similarly attenuated in PTX-treated cultures. These results together with our previous physiologic and biochemical analyses of adenylate cyclase (AC) and cyclic AMP (cAMP) activities in cord-ganglion cultures suggest that the neuromodulatory effects of opioid, monoaminergic and muscarinic agonists on primary afferent networks in the spinal cord may be mediated by binding to neuronal receptor subtypes that are negatively coupled via Gi to a common pool of AC.