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724619 
Journal Article 
Local administration of a corticotropin - releasing factor antagonist in the locus coeruleus prevents swim stress - induced increases in norepinephrine efflux in the rat frontal cortex 
Page, ME; Szeliga, PJ; Fitzgerald, P 
2003 
2003 
Abstract 
Stress is known to be a substantial risk factor in the vulnerability to drug abuse and relapse. Additionally, stress is clearly a precipitating factor in the development of affective disorders. Animal models that employ exposure to stressors are utilized to gain insight to understanding the pathophysiology of psychiatric disorders and to help direct the development of therapeutic interventions. In a previous study, we demonstrated increased extracellular norepinephrine (NE) evoked by exposure to the forced swimming test (FST) on two consecutive days. The typical behavioral profile observed on Day 1 of the FST is mixed activity consisting of nearly equal time spent swimming, climbing and immobile. On Day 2, immobility is the predominant behavior. Immobility is significantly reduced by treatment with antidepressant compounds in the intervening 24 hrs between tests. In the present study, we have examined the role of the stress-related neurotransmitter, corticotropin-releasing factor (CRF) in regulation of locus coeruleus (LC) activity during the FST. Microdialysis probes and LC guide cannulae were implanted under chloral hydrate anesthesia 16-18 hrs prior to experimentation. Following at least 2 hrs of baseline sampling, local infusions of d-Phe12-41 were made into the LC region. Rats were placed into the swim chamber 20 minutes after infusion. Activity was videotaped during the 15 min exposure to the FST for subsequent analysis. Local infusion of d-Phe12-41 in the LC region attenuated the increase in extracellular NE observed in the frontal cortex and was associated with a behavioral profile similar to that seen on Day 2 in untreated animals i.e., greater immobility and reduced swimming and climbing. These data suggest that CRF activates LC neurons during stress and that the increase in NE is involved in behavioral activation 
Muridae--Rodentia,Mammalia,Vertebrata,Chordata,Animalia