Hippocampal norepinephrine-like voltammetric responses following infusion of corticotropin-releasing factor into the locus coeruleus

Intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) increases the activity of noradrenergic neurons in the locus c oeruleus (LC) assessed by electrophysiological and neurochemical studies, I t has been suggested that this effect of i.c.v. CRF is exerted directly on LC noradrenergic (LC-NE) neurons, Infusion of CRF directly into the LC incr eases cortical and hippocampal release of norepinephrine (NE) as indicated by in vivo microdialysis studies, but the electrophysiological studies have shown both increases and decreases. The present study used in vivo voltamm etry to study changes in the extracellular concentrations of NE in the rat hippocampus in response to infusion of CRF (100 ng) into the LC, When the i nfusion cannula was located in or very close to the LC, the immediate respo nse to CRF was a small decrease in the NE-like oxidation current, followed by a robust increase after about 6-7 min. The oxidation current reached a p eak around 13 min and returned to baseline by about 30 min after CRF infusi on, By contrast with CRF, infusion of glutamate into the LC increased the o xidation current with a delay of around 30 a and a peak within 90 s, The re sponses to LC infusion of CRF in rats treated with DSP-4 to deplete hippoca mpal NE were substantially smaller than those in untreated rats, suggesting that the oxidation signals in untreated rats reflected changes in concentr ations of NE, The response to glutamate was markedly augmented by pretreatm ent with the NE reuptake inhibitor, desmethylimipramine, suggesting that th e observed responses reflected changes in NE, Infusion of the same dose of CRF into brain structures outside the LC did not elicit consistent changes in oxidation current in the hippocampus, The time course of the responses t o CRF is compatible with previously reported electrophysiological responses of LC-NE neurons to CRF and with neurochemical evidence indicating that CR F can affect the activity of LC-NE neurons. The results indicate that CRF m ay act in or close to the LC to induce release of hippocampal NE, but the d elayed response to CRF compared with that to glutamate, suggests that CRF d oes not directly activate LC-NE neurons. (C) 2000 Elsevier Science Inc.