Discharge activities of neurons in the nucleus paragigantocellularis during the development of morphine tolerance and dependence: a single unit study in chronically implanted rats.

Abstract

The nucleus paragigantocellularis (PGi) has been proposed to play a role in opiate dependence/withdrawal. In the present study, we examined the discharge activity of PGi neurons before and after the development of morphine tolerance/dependence in rats. A multi-wire electrode was chronically implanted in the PGi, which allowed us to monitor the effects of both acute and chronic morphine treatments on the activity of PGi neurons recorded from the same site. We found that acute morphine excited, inhibited or had no effect on 36%, 35% or 29% of PGi neurons (N=556), respectively. After 3 days of continuous morphine infusion, which led to morphine tolerance/dependence, the firing rates of both excitatory and inhibitory PGi neurons returned to pre-morphine treatment levels, indicating that the PGi neurons developed tolerance to both excitatory and inhibitory effects of morphine. Naltrexone-precipitated withdrawal from chronic morphine treatment also induced heterogeneous responses in the PGi. On a site-by-site basis, most of the sites that showed excitatory response to acute morphine exhibited inhibitory response during withdrawal, and all the sites that showed inhibitory response to acute morphine exhibited excitatory response during withdrawal. Correlation analysis further quantitatively showed that PGi neurons' responses to acute morphine and that during withdrawal were inversely correlated with a correlation coefficient of 0.73, suggesting that adaptations in the PGi during the development of morphine dependence share common neural mechanisms with the acute effect of morphine. These results provide new insights into the role of the PGi in the development of morphine tolerance/dependence.