Delivery of neuropeptide Y (NPY) to the brain by intranasal infusion soon after traumatic stress has shown therapeutic potential, and prevented development of many behavioral and neuroendocrine impairments in the single prolonged stress (SPS) animal model of PTSD. Therefore, we examined whether the Y1R preferring agonist [Leu(31)Pro(34)]NPY is sufficient to prevent development of SPS induced depressive-like behavioral changes, and hypothalamic gene expression as obtained with intranasal NPY intervention. Male Sprague-Dawely rats were given intranasal infusion of either NPY (150 μg/rat), a low (68 μg /rat), or high (132 μg/rat) dose of [Leu(31)Pro(34)]NPY or vehicle immediately following the last SPS stressor, left undisturbed for 1 week and then tested for depressive-like behavior together with naïve unstressed controls. Vehicle treated animals had elevated immobility forced swim test (FST) and reduced sucrose preference, which were not observed in animals given NPY or the higher dose of [Leu(31)Pro(34)]NPY. This dose of [Leu(31)Pro(34)]NPY, like NPY, also prevented the SPS-elicited induction of CRF mRNA in the mediobasal hypothalamus. However, [Leu(31)Pro(34)]NPY did not prevent, but rather enhanced, the SPS-triggered induction of GR and FKBP5 mRNA levels in the mediobasal hypothalamus. Thus, [Leu(31)Pro(34)]NPY may be as effective as NPY and displays therapeutic potential for preventing development of depressive-like behaviors and dysregulation of the CRF/HPA system in PTSD. However, due to its different effects compared to NPY on GR and FKBP5 a broader agonist, such as NPY, may be more desirable.
Pharmacology, Toxicology and Pharmaceutical Science
4
10%
Agricultural and Biological Sciences
3
8%
Biochemistry, Genetics and Molecular Biology
2
5%
Other
5
13%
Unknown
11
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 April 2017.
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#20,660,571
of 25,382,440 outputs
Outputs from Frontiers in Neuroscience
#9,459
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Outputs of similar age
#249,043
of 324,249 outputs
Outputs of similar age from Frontiers in Neuroscience
#177
of 210 outputs
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