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Sex differences in the ontogeny of CRF receptors during adolescent development in the dorsal raphe nucleus and ventral tegmental area
Author(s) -
Lukkes Jodi L.,
Norman Kevin J.,
Meda Shirisha,
Andersen Susan L.
Publication year - 2016
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21882
Subject(s) - tph2 , dorsal raphe nucleus , ventral tegmental area , monoaminergic , raphe nuclei , medicine , endocrinology , receptor , neuroscience , psychology , biology , serotonin , dopamine , serotonergic , dopaminergic
Interactions between corticotropin‐releasing factor (CRF) and monoaminergic systems originating from the dorsal raphe nucleus (DR) and ventral tegmental area (VTA) have been implicated in the etiology and pathophysiology of several stress‐related neuropsychiatric disorders such as depression and substance abuse. Sub‐regions within the DR and VTA give rise to specific projections that have unique roles in limbic‐ and reward‐related behaviors. Given that these disorders typically emerge during adolescence, it is surprising that few studies have examined the age‐, sex‐, and region‐dependent expression of CRF receptors throughout multiple stages of adolescence in these stress‐relevant circuits. To determine the ontogeny of CRF receptors during adolescent development, three regions of the DR (dorsal, caudal, and ventrolateral parts) and the posterior VTA were microdissected from Sprague‐Dawley male and female rats on postnatal day (P) 25, P35, P42, P56, and P90. Tissue was processed and analyzed with qRT‐PCR to measure CRF 1 and CRF 2 receptors. The serotonin and catecholamine enzymes in the DR and VTA, tryptophan hydroxylase 2 (TPH2) and tyrosine hydroxylase, respectively, were also analyzed for maturational differences. This study identified that CRF 1 receptors are lower in males than females within the dorsal, ventrolateral region of the DR (DRVL), which is involved in anxiety‐, stress‐, and panic‐related responses. Females had higher CRF 2 receptors compared to males in the DRVL only. Levels of TPH2 mRNA in the DRVL were overproduced transiently in females before declining into adulthood. These fundamental studies suggest that sex differences in CRF receptors should be considered when examining stress‐related neuropsychiatric disorders and their treatment. Synapse 70:125–132, 2016. © 2016 Wiley Periodicals, Inc.