GABA RECEPTOR-LINKED CHLORIDE CHANNELS AND THE BEHAVIORAL-EFFECTS OF NALTREXONE IN RATS

The present study was conducted to determine whether the effects of na ltrexone on schedule-controlled behavior in rats were mediated, at lea st in part, by the GABAergic system. Because the enhanced sensitivity that has been shown to occur following naltrexone treatment might alte r the effects of the treatment compounds, a variety of compounds inter acting with the GABA system were tested in both sensitized and nonsens itized animals. Of all the compounds tested in this manner, only the d ose-effect function for the GABAA agonist muscimol was altered by the naltrexone treatment, with the higher doses of muscimol producing resp onse-rate decreasing effects only in naltrexone-sensitized rats. In th e naltrexone-treated animals, these same GABA agonists and antagonists were used as pretreatments prior to the determination of the naltrexo ne dose-effect function. Although shifts in the naltrexone dose-effect function were observed, the effects were not consistent either within or across receptor class. In contrast, the chloride-channel antagonis t picrotoxin clearly shifted the naltrexone dose-effect function in se nsitized animals to the left, while the chloride-channel facilitator p entobarbital shifted the function to the right. These results indicate that the effects of naltrexone are at least partially mediated by an action at the GABA-linked chloride channel, rather than directly at th e GABA receptor.