Studies on the interaction between ICV effects of CRF and CNS noradrenaline depletion

The role of an intact locus coeruleus (LC) noradrenergic system for the central effects of corticotropin-releasing factor (CRF) was studied. Rats were treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a highly selective noradrenergic neurotoxin permanently affecting mainly the LC system. This procedure did not affect the activation of the sympathetic nervous system, as measured by plasma catecholamine levels, after either intracerebroventricular (ICV) or intraperitoneal (IP) administration of 8-micrograms CRF. Neither was the increased emotionality seen in an open field test after ICV injection of CRF altered. However, the ulceroprotective effect of 8-micrograms CRF ICV during a 2-hr water restraint stress was significantly antagonized by pretreatment with DSP-4, while CRF did exhibit an ulceroprotective effect after IP administration to DSP-4-treated animals. Our data indicate that the ulceroprotective effect of CRF under restraint stress is, at least partly, dependent on an intact locus coeruleus noradrenergic system.