MICROINFUSION OF CORTICOTROPIN-RELEASING FACTOR INTO THE LOCUS COERULEUS/SUBCOERULEUS NUCLEI STIMULATES COLONIC MOTOR FUNCTION IN RATS

Convergent evidence indicates that brain corticotropin-releasing factor (CRF) participates in stress-related alterations of gastric and colonic motor function. CRF in the locus coeruleus has been shown to induce anxiogenic response. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CRF to alter gastric and colonic transit was investigated in conscious, chronically cannulated rats. CRF (0.2 nmol) microinjected into the LC/SC did not influence gastric emptying of a non-caloric semi-liquid meal while stimulating colonic transit by 57% as assessed by the geometric center in fasted rats. Under the same conditions, i.c.v. injection of CRF (0.2 nmol) delayed gastric emptying by 31% and increased colonic transit by 103%. When colonic transit was evaluated as the time of appearance in the feces of a marker placed in the proximal colon, CRF (0.2 nmol) injected into the LC/SC or i.c.v. stimulated colonic transit by 77% and 48% respectively and fecal output/6h by 3.8 and 2.8 fold respectively. Microinjection of CRF into the medial and lateral parabrachial nucleus, postero-dorsal tegmental nucleus, dorsomedial tegmental area and the ventral part of the nucleus subcoeruleus did not influence colonic transit. These data indicate that CRF acts in the LC/SC to induce a long lasting stimulation of colonic transit and bowel discharge without influencing gastric emptying. These findings suggest a possible role of the LC/SC in the regulation of colonic motor function and of endogenous CRF at these sites in the stress-related activation of colonic motor function.