Evidence for functional release of endogenous opioids in the locus ceruleus during stress termination

Endogenous opioids target noradrenergic locus ceruleus (LC) neurons and pot ently inhibit LC activity. Nonetheless, it has been difficult to demonstrat e functional regulation of the LC-noradrenergic system by endogenous opioid s because of the lack of effect of opiate antagonists. The present findings provide evidence that endogenous opioids regulate LC neuronal activity dur ing the termination of a stressor. LC neuronal discharge was recorded from halothane-anesthetized rats before, during, and after hypotensive stress el icited by intravenous nitroprusside infusion. In naive rats, mean arterial blood pressure was temporally correlated with LC activity such that hypoten sion was associated with increased LC discharge and a return to the normote nsive state was associated with a decrease in LC discharge below pre-stress values. After microinfusion of an antagonist of the stress neuropeptide co rticotropin-releasing factor (CRF) into the LC, the increase in LC discharg e associated with hypotension was prevented, whereas LC inhibition associat ed with termination of the challenge occurred at an earlier time and was of a greater magnitude. In contrast, microinfusion of naloxone into the LC co mpletely abolished LC inhibition associated with termination of the stresso r. Naloxone microinfusion did not prevent LC inhibition associated with hyp ertension produced by intravenous vasopressin administration, suggesting th at endogenous opioids may be selectively engaged during the termination of hypotensive stress. These results provide evidence for a functional release of endogenous opioids within the LC. This action of endogenous opioids may serve to counterbalance excitatory effects of CRF on the LC-norepinephrine system, thereby limiting its activation by stress.