The role of orexin and serotonin 1A receptor in the expression or modulation of the cardiovascular and behavioural components of psychological and physical stress

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Copyright: Luong, Leanne
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Abstract
This thesis attempted to identify the site(s) of action of orexin and 5HT1A receptor agonists in the central network that mediate/modulate the cardiovascular and behavioural changes evoked by psychological and physical stress. Central blockade of orexin receptors with Almorexant in the lateral ventricle significantly reduced the locomotor response to Novelty stress but did not significantly reduce the associated cardiovascular response. Comparison of the effect of orexin-A in the lateral ventricle, fourth ventricle and thoracic cord showed that orexin injections in the upper thoracic cord could evoke substantial cardiovascular effects, comparable to those evoked from the fourth and lateral ventricle, suggesting that orexin could act at spinal level to mediate the cardiovascular effects of stress. This was confirmed by showing high levels of Fos expression in orexin neurons retrogradely labelled from the upper thoracic cord after Fear, Novelty and Exercise. Finally, orexin-A in the medullary raphe evoked clear cardiovascular effects, indicating that the medullary raphe could also be an important supraspinal site of action of orexin in the cardiovascular response to stress. The 5HT1A receptor agonist 8-OH-DPAT evoked greater reduction in the cardiovascular response to Novelty, Restraint, Fear and Cold after injection in the fourth ventricle than after injections in the lateral ventricle. This indicates that the lower brainstem is likely the main site of action of 8-OH-DPAT for the cardiovascular component of these stressors, suggesting a direct sympathoinhibitory effect. However, the reduction of the freezing response evoked by Fear was greater after lateral ventricle than fourth ventricle injections, suggesting an anxiolytic effect in the forebrain and/or midbrain region. Thus, this thesis has identified the most probable site(s) of action of orexin and 5HT1A agonists for the cardiovascular response to stress. Orexin is likely to have a direct action in the upper thoracic cord together with an indirect action in the lower brainstem, most probably in the medullary raphe. 5HT1A agonists appear to act preferentially in the lower brainstem, most probably in the medullary raphe also. In contrast, both systems preferentially act on forebrain/midbrain regions to mediate/modulate the behavioural response to stress.
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Author(s)
Luong, Leanne
Supervisor(s)
Carrive, Pascal
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Publication Year
2012
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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