Hippocampal noradrenergic responses to CRF injected into the locus coeruleus of unanesthetized rats

Intracerebral administration of corticotropin-releasing factor (CRF) activates cerebral noradrenergic neurons. Direct infusion of CRF into the locus coeruleus (LC) increases norepinephrine (NE) release in the cortex and hippocampus as assessed by in vivo microdialysis. In a recent study using in vivo chronoamperometry in anesthetized rats, CRF injected into the LC increased apparent NE release in the hippocampus, but did so after a significant delay, much longer than observed following infusion of glutamate into the same site. Because this delay may have been an artifact of the urethane anesthesia, we developed a method for chronoamperometric recording from the hippocampus of unanesthetized rats. CRF infusion into the LC of such animals induced an increase in the apparent release of hippocampal NE after a mean delay of about 7 min, reached a peak around 16 min after CRF, and dissipated within 30 min. Thus the response closely resembled that previously reported in urethane-anesthetized rats. As in anesthetized rats, glutamate infused into the same site resulted in a much more rapid response (starting within 1 min and with a peak around 7 min). These results suggest that the urethane anesthesia does not substantially alter hippocampal NE release following infusion of CRF into the LC, and that the relatively long delay in the response is not an artifact of the anesthesia. The large differences in the responses to glutamate and CRF suggest that the effects of CRF are not exerted directly on receptors on LC neurons, and more likely reflect indirect actions on other cells in this region.