Investigating Tryptophan Hydroxylase Immunoreactivity in the Dorsal Raphe of Rats Exposed to Early Adversity

2018 ◽  
Author(s):  
Katheron Intson
Keyword(s):  
Tryptophan Hydroxylase ◽  
Research Question ◽  
Dorsal Raphe ◽  
Female Rats ◽  
Early Adversity ◽  
Fiber Density ◽  
Stress Study ◽  
Two Factors ◽  
And Function ◽  
Dorsal Raphé

Prior studies link anxiety to alterations in serotonergic neurotransmission. Tao and Menard (unpublished data) found that female rats exposed to intermittent physical stress during early adolescence display greater levels of anxiety-like behaviours when tested as adults in social interaction tests. Interestingly, these behavioural changes were associated with changes in serotonin (5-HT) fiber density in the medial prefrontal cortex. Whether these changes in 5-HT fibre density are accompanied by changes in the number of 5-HT-producing cells in the dorsal raphe is not known. To examine this research question, tryptophan-hydroxylase (TPH) immunoreactivity (-IR) was used to label 5-HT cells in the dorsal raphe. Half the animals from the original adolescent stress study were exposed to IPS, and the remaining animals were handled only, serving as the control (CON) group. In adulthood, half of each of those groups were tested in the SI test. The remaining animals were not behaviourally tested, serving as home-cage controls (HCC). A two-factor analysis of variance will be performed with Treatment (IPS vs CON) and Testing (SI vs HCC) as the two factors. It is expected that, regardless of Testing, IPS rats will display higher levels of TPH-IR in the dorsal raphe than no-stress controls. The number of TPH-IR-positive cells will also be correlated with archival behavioural data. It is expected that that higher levels of TPH-IR will be associated with higher levels of anxiety-like behaviour. This study provides insights into the role that early adversity plays in shaping the structure and function of the brain’s serotonergenic system.

scholarly journals Early adolescent adversity alters periaqueductal gray/dorsal raphe threat responding in adult female rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mahsa Moaddab ◽  
Kristina M. Wright ◽  
Michael A. McDannald
Keyword(s):  
Single Unit ◽  
Periaqueductal Gray ◽  
Dorsal Raphe ◽  
Female Rats ◽  
Early Adolescent ◽  
Early Adversity ◽  
Single Unit Activity ◽  
Adult Rats ◽  
Long Evans ◽  
Dorsal Raphé

Abstract Early adolescent adversity increases adult risk for anxiety disorders. The ventrolateral periaqueductal gray (vlPAG) and neighboring dorsal raphe (DR) are integral to threat prediction, and are responsive to acute stressors. Here, we tested the hypothesis that early adolescent adversity reshapes vlPAG/DR threat-related cue activity and threat probability signaling. Female, Long Evans rats experienced a battery of adverse adolescent experiences (n = 12), while controls did not (n = 8). Single-unit activity was recorded 50 + days following the final adverse experience, when the adult rats received fear discrimination consisting of danger, uncertainty and safety cues. Despite achieving fear discrimination that was equivalent to controls, vlPAG/DR threat responding was altered in adverse-experienced rats. Early adolescent adversity resulted in a greater proportion of cue-responsive neurons. Cue-excited neurons showed greater increases in firing and cue-inhibited neurons showed greater decreases. Even more, early adversity reduced flexible, threat probability signaling by cue-excited neurons and promoted more rigid, fear output signaling by cue-inhibited neurons. The results reveal long-lasting changes in vlPAG/DR threat responding resulting from early adolescent adversity.

scholarly journals Dorsal raphe serotonin neurotransmission is required for the expression of nursing behavior and for pup survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aude Muzerelle ◽  
Mariano Soiza-Reilly ◽  
Cornelia Hainer ◽  
Pierre-Louis Ruet ◽  
Klaus-Peter Lesch ◽  
...  
Keyword(s):  
Tryptophan Hydroxylase ◽  
Dorsal Raphe ◽  
Normal Mammary Gland ◽  
Knock Out ◽  
Maternal Experience ◽  
Pup Retrieval ◽  
Pup Survival ◽  
Gland Development ◽  
Severe Growth ◽  
Dorsal Raphé

AbstractProper maternal care is an essential factor of reproductive success in mammals, involving a repertoire of behaviors oriented toward the feeding and care of the offspring. Among the neurotransmitters involved in the initiation of these behaviors, serotonin (5-HT) seems to play an important role. Here we compared pup-oriented maternal behaviors in mice with constitutive 5-HT depletion, the tryptophan hydroxylase 2-knock-out (Tph2-KO) and the Pet1-KO mice. We report that the only common pup-oriented defect in these 2 hyposerotoninergic models is a defective nursing in parturient mice and altered nursing-like (crouching) behavior in virgin mice, while pup retrieval defects are only present in Tph2-KO. Despite a normal mammary gland development and milk production, the defect in appropriate nursing is responsible for severe growth retardation and early lethality of pups born to hyposerotonergic dams. This nursing defect is due to acute rather constitutive 5-HT depletion, as it is reproduced by adult knockdown of Tph2 in the dorsal raphe nucleus in mothers with a prior normal maternal experience. We conclude that 5-HT innervation from the dorsal raphe is required for both the initiation and maintenance of a normal nursing behavior. Our findings may be related to observations of reduced maternal/infant interactions in human depression.

Effect of fluoxetine on the expression of tryptophan hydroxylase and 14-3-3 protein in the dorsal raphe nucleus and hippocampus of rat

2012 ◽  
Vol 43 (2) ◽  
pp. 96-102 ◽  
Author(s):  
Mi Ran Choi ◽  
Sejin Hwang ◽  
Geu Meum Park ◽  
Kyung Hwa Jung ◽  
Seok Hyeon Kim ◽  
...  
Keyword(s):  
Tryptophan Hydroxylase ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Dorsal Raphé

More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides

2005 ◽  
Vol 1041 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Maura Boldrini ◽  
Mark D. Underwood ◽  
J. John Mann ◽  
Victoria Arango
Keyword(s):  
Tryptophan Hydroxylase ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Dorsal Raphé

scholarly journals Modulation of the firing activity of female dorsal raphe nucleus serotonergic neurons by neuroactive steroids

2004 ◽  
Vol 182 (1) ◽  
pp. 11-21 ◽  
Author(s):  
M Robichaud ◽  
G Debonnel
Keyword(s):  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Neuronal Firing ◽  
Neuroactive Steroids ◽  
Female Rats ◽  
Firing Activity ◽  
Sigma 1 ◽  
Dorsal Raphé

Important gender differences in mood disorders result in a greater susceptibility for women. Accumulating evidence suggests a reciprocal modulation between the 5-hydroxytryptamine (5-HT) system and neuroactive steroids. Previous data from our laboratory have shown that during pregnancy, the firing activity of 5-HT neurons increases in parallel with progesterone levels. This study was undertaken to evaluate the putative modulation of the 5-HT neuronal firing activity by different neurosteroids. Female rats received i.c.v. for 7 days a dose of 50 micro g/kg per day of one of the following steroids: progesterone, pregnenolone, 5beta-pregnane-3,20-dione (5beta-DHP), 5beta-pregnan-3alpha-ol,20-one, 5beta-pregnan-3beta-ol,20-one, 5alpha-pregnane-3,20-dione, 5alpha-pregnan-3alpha-ol,20-one (allopregnanolone, 3alpha,5alpha-THP), 5alpha-pregnane-3beta-ol,20-one and dehydroepiandrosterone (DHEA). 5beta-DHP and DHEA were also administered for 14 and 21 days (50 micro g/kg per day, i.c.v.) as well as concomitantly with the selective sigma 1 (sigma1) receptor antagonist NE-100. In vivo, extracellular unitary recording of 5-HT neurons performed in the dorsal raphe nucleus of these rats revealed that DHEA, 5beta-DHP and 3alpha,5alpha-THP significantly increased the firing activity of the 5-HT neurons. Interestingly, 5beta-DHP and DHEA showed different time-frames for their effects with 5beta-DHP having its greatest effect after 7 days to return to control values after 21 days, whereas DHEA demonstrated a sustained effect over the 21 day period. NE-100 prevented the effect of DHEA but not of 5beta-DHP, thus indicating that its sigma1 receptors mediate the effect of DHEA but not that of 5beta-DHP. In conclusion, our results offer a cellular basis for potential antidepressant effects of neurosteroids, which may prove important particularly for women with affective disorders.

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