Details

Autor(en) / Beteiligte

• Rosario, Lilliam Annette

Titel

Cellular bases of stress reactivity: Locus coeruleus

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1997

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Individual differences in the response of organisms to stressful stimuli have been well documented in humans, as well as rats. At present, the biological substrates underlying these differences are not well understood. This thesis develops the argument that the locus coeruleus-norepinephrine system may serve as a neural substrate underlying differential behavioral reactivity to stress. Two rat models were used to investigate the relationship between the evoked responsiveness of the locus coeruleus-norepinephrine system and behavioral reactivity to stress. One population comprised individuals selected from an outbred Sprague Dawley strain differing in the locomotor activity in response to a novel open field. Inbred Fischer and Lewis rat strains were also used as a model based on previously demonstrated behavioral and neuroendocrine differences between these strains. In chapter 1, it was demonstrated that the locomotor response to a novel open field is a stable individual trait and can be used as index of the behavioral response to stress. This trait was used to select individuals from an outbred strain that varied in the behavioral response to stress. Then, using in vivo microdialysis, it was determined that individuals with low reactivity to stress exhibit blunted noradrenergic responses to a behavioral, but not to pharmacological challenge. In Chapter 2, the behavioral characterization was extended to Fischer and Lewis rats. Using in vivo microdialysis, it was demonstrated that Lewis rats, the hypo-reactive strain, exhibit a blunted noradrenergic response to a behavioral and pharmacological challenge. Moreover, a failure of stressful challenges to elevate indices of the biosynthesis rate of norepinephrine in Lewis rats indicated that differences in tyrosine hydroxylation contribute to the profiles of norepinephrine release observed in Fischer and Lewis rats. In Chapter 3, a possible physiological basis for differences in evoked norepinephrine release and synthesis was investigated. Direct sequencing of the tyrosine hydroxylase gene did not reveal polymorphisms between F344 and LEW strains suggesting that differences in tyrosine hydroxylation between these strains are not due to sequence variations in the coding regions of the gene. In sum, these results support the hypothesis that the locus coeruleus-norepinephrine system serves as a neural substrate underlying differential behavioral reactivity to stress.