Medial septal injection of naloxone elevates acetylcholine release in the hippocampus and induces behavioral seizures in rats

Abstract

The effects of injections of naloxone, a universal opioid receptor antagonist, into the medial septal nucleus on hippocampal acetylcholine (ACh) release and behavior were investigated in freely moving rats by means of the microdialysis method. The injection of naloxone (2, 10 and 20 μg) produced a marked increase in hippocampal ACh release in a dose-dependent manner. These effects of naloxone were reversed by the post-injection of [ d-Ala 2, N-Me-Phe 4,Gly-ol]-enkephalin (DAGO; 10 μg), an opioid μ receptor agonist. Furthermore, basal release of hippocampal ACh was significantly reduced by the injection of DAGO alone. It was also found that rats given an injection of naloxone showed an increase in motor activity and occasionally exhibited behavioral seizures. These effects of naloxone were also reversed by the post-injection of DAGO. The present results suggest that endogenous opioids tonically inhibit the activity of septo-hippocampal cholinergic neurons via mediation of μ opioid receptors in the medial septal nucleus. They also suggest that endogenous opioids modulate the incidence of seizures, at least in part, through opioid μ receptors in the medial septal nucleus.