scholarly journals 5-HT2A receptor loss does not alter acute fluoxetine-induced anxiety and exhibit sex-dependent regulation of cortical immediate early gene expression

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Minal Jaggar ◽  
Toshali Banerjee ◽  
Noelia Weisstaub ◽  
Jay A. Gingrich ◽  
Vidita A. Vaidya

Abstract Background: Acute treatment with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (Flx), induces anxiety-like behavioral effects. The serotonin2A receptor (5-HT2A) is implicated in the modulation of anxiety-like behavior, however its contribution to the anxiogenic effects of acute Flx remains unclear. Here, we examined the role of the 5-HT2A receptor in the effects of acute Flx on anxiety-like behavior, serum corticosterone levels, neural activation and immediate early gene (IEG) expression in stress-responsive brain regions, using 5-HT2A receptor knockout (5-HT2A−/−) mice of both sexes. Methods: 5-HT2A−/− and wild-type (WT) male and female mice received a single administration of Flx or vehicle, and were examined for anxiety-like behavior, serum corticosterone levels, FBJ murine osteosarcoma viral oncogene homolog peptide (c-Fos) positive cell numbers in stress-responsive brain regions of the hypothalamus and prefrontal cortex (PFC), and PFC IEG expression. Results: The increased anxiety-like behavior and enhanced corticosterone levels evoked by acute Flx were unaltered in 5-HT2A−/− mice of both sexes. 5-HT2A−/− female mice exhibited a diminished neural activation in the hypothalamus in response to acute Flx. Further, 5-HT2A−/− male, but not female, mice displayed altered baseline expression of several IEGs (brain-derived neurotrophic factor (Bdnf), Egr2, Egr4, FBJ osteosarcoma gene (Fos), FBJ murine osteosarcoma viral oncogene homolog B (Fosb), Fos-like antigen 2 (Fosl2), Homer scaffolding protein (Homer) 1-3 (Homer1-3), Jun proto-oncogene (Jun)) in the PFC. Conclusion: Our results indicate that the increased anxiety and serum corticosterone levels evoked by acute Flx are not influenced by 5-HT2A receptor deficiency. However, the loss of function of the 5-HT2A receptor alters the degree of neural activation of the paraventricular nucleus (PVN) of the hypothalamus in response to acute Flx, and baseline expression of several IEGs in the PFC in a sexually dimorphic manner.

2019 ◽  
Vol 236 (12) ◽  
pp. 3525-3539 ◽  
Author(s):  
Bruno G. Berardino ◽  
Estefanía A. Fesser ◽  
Laura M. Belluscio ◽  
Octavio Gianatiempo ◽  
Nicolás Pregi ◽  
...  

Hippocampus ◽  
2018 ◽  
Vol 29 (6) ◽  
pp. 481-490
Author(s):  
Wing K. L. Witharana ◽  
Benjamin J. Clark ◽  
Vivek Trivedi ◽  
Lilia Mesina ◽  
Bruce L. McNaughton

2009 ◽  
Vol 33 (6) ◽  
pp. 945-969 ◽  
Author(s):  
Catherine Vilpoux ◽  
Vincent Warnault ◽  
Olivier Pierrefiche ◽  
Martine Daoust ◽  
Mickael Naassila

2019 ◽  
Vol 372 ◽  
pp. 112006
Author(s):  
Jonathan M. Turner ◽  
Ryan G. Will ◽  
Eric A. Harvey ◽  
Tomoko Hattori ◽  
Daniel J. Tobiansky ◽  
...  

2005 ◽  
Vol 58 (3-4b) ◽  
pp. 218-233 ◽  
Author(s):  
John P. Aggleton ◽  
Malcolm W. Brown

The perirhinal cortex and hippocampus have close anatomical links, and it might, therefore, be predicted that they have close, interlinked roles in memory. Lesion studies have, however, often failed to support this prediction, providing dissociations and double dissociations between the two regions on tests of object recognition and spatial memory. In a series of rat studies we have compared these two regions using the expression of the immediate early gene c- fosas a marker of neuronal activity. This gene imaging approach makes it possible to assess the relative involve-ment of different brain regions and avoids many of the limitations of the lesion approach. A very consistent pattern of results was found as the various hippocampal subfields but not the peri-rhinal cortex show increased c- fosactivity following tests of spatial learning. In contrast, the perirhinal cortex but none of the hippocampal subfields show increased c- fosactivity when presented with novel rather than familiar visual objects. When novel scenes are created by the spatial rearrangement of familiar objects it is the hippocampus and not the perirhinal cortex that shows c- foschanges. This double dissociation for gene expression accords with that found from lesion studies and highlights the different contributions of the perirhinal cortex and hippocampus to memory.


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