Specific versus non-specific actions of opioids on hippocampal neurones in the rat brain.

An investigation has been made into the pharmacological specificity of the actions of microelectrophoretically applied opioids on neurones in the rat hippocampus, a structure containing a low concentration of specific receptors for these substances. The majority of hippocampal neurones remained unaffected by morphine or enkephalin. Some neurones, however, displayed either inhibitory or excitatory responses to the opioids. Of the inhibitory effects, a few appeared to be specific, in that they could be antagonized by naloxone, but most of the other inhibitory responses were found to be potentiated by this drug. Similarly, naloxone not only failed to antagonize, but frequently potentiated the excitatory responses to the opioids. Further evidence for the predominantly non-specific nature of the responses of hippocampal neurones to opioids was provided by experiments with the stereoisomers levorphanol and dextrorphan. Neurones could be found which were either inhibited or excited by both enantiomers. Stereospecific responses, when observed, were inhibitory. Although non-specific, the excitatory effects of enkephalin and morphine on hippocampal neurones were greatly reduced in morphine tolerant/dependent rats. Indeed, in the hippocampus of these animals, the opioids had predominantly inhibitory effects which were potentiated, not antagonized, by naloxone. It is concluded that the low concentration of opiate receptors in the rat hippocampus renders neurones within this structure sensitive to a variety of nonspecific opioid actions.