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Endocrinology. 2014 Aug;155(8):2996-3004. doi: 10.1210/en.2013-1411. Epub 2014 May 30.

The medial amygdala-medullary PrRP-synthesizing neuron pathway mediates neuroendocrine responses to contextual conditioned fear in male rodents.

Author information

1
Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University, Shimotsuke-shi, Tochigi-ken 329-0498, Japan.

Abstract

Fear responses play evolutionarily beneficial roles, although excessive fear memory can induce inappropriate fear expression observed in posttraumatic stress disorder, panic disorder, and phobia. To understand the neural machineries that underlie these disorders, it is important to clarify the neural pathways of fear responses. Contextual conditioned fear induces freezing behavior and neuroendocrine responses. Considerable evidence indicates that the central amygdala plays an essential role in expression of freezing behavior after contextual conditioned fear. On the other hand, mechanisms of neuroendocrine responses remain to be clarified. The medial amygdala (MeA), which is activated after contextual conditioned fear, was lesioned bilaterally by infusion of N-methyl-d-aspartate after training of fear conditioning. Plasma oxytocin, ACTH, and prolactin concentrations were significantly increased after contextual conditioned fear in sham-lesioned rats. In MeA-lesioned rats, these neuroendocrine responses but not freezing behavior were significantly impaired compared with those in sham-lesioned rats. In contrast, the magnitudes of neuroendocrine responses after exposure to novel environmental stimuli were not significantly different in MeA-lesioned rats and sham-lesioned rats. Contextual conditioned fear activated prolactin-releasing peptide (PrRP)-synthesizing neurons in the medulla oblongata. In MeA-lesioned rats, the percentage of PrRP-synthesizing neurons activated after contextual conditioned fear was significantly decreased. Furthermore, neuroendocrine responses after contextual conditioned fear disappeared in PrRP-deficient mice. Our findings suggest that the MeA-medullary PrRP-synthesizing neuron pathway plays an important role in neuroendocrine responses to contextual conditioned fear.

PMID:
24877622
PMCID:
PMC4207914
DOI:
10.1210/en.2013-1411
[Indexed for MEDLINE]
Free PMC Article

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