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Pharmacopsychiatry 2016; 49(04): 142-145
DOI: 10.1055/s-0042-105018
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Conserved Hypothalamic c-Fos Activation Pattern Induced by the mGlu5 Receptor Antagonist MPEP during Peri-pubertal Development in Mice

I. Inta
1   RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
2   Division of Pediatric Endocrinology, University Children’s Hospital Heidelberg, Germany
,
M. Bettendorf
2   Division of Pediatric Endocrinology, University Children’s Hospital Heidelberg, Germany
,
P. Gass
1   RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

received 16 November 2015
revised 07 March 2016

accepted 09 March 2016

Publication Date:
21 April 2016 (online)

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Abstract

Introduction: 2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a selective mGlu5 receptor (mGluR5) antagonist intensively studied as potential novel anxiolytic drug. In the adult, MPEP activates stress-related areas, including the paraventricular nucleus of the hypothalamus (PVNh). However, it is unknown if MPEP targets similar structures in the juvenile brain as well.

Methods: Here we examined by immunohistochemical methods the induction pattern of the neuronal activity marker c-Fos by MPEP at peri-pubertal stages (postnatal day P16, P24, P32 and P40) in C57BL6/N mice.

Results: Despite the previously reported sharply diminished hypothalamic mGluR5 expression during postnatal development, we found a highly conserved PVNh activation by MPEP together with c-Fos expression in the extended amygdala. Interestingly, MPEP also robustly activated the paraventricular nucleus of the thalamus (PVT) and suprachiasmatic nucleus (SCN), regions associated with the modulation of circadian rhythms.

Discussion: These results indicate a conserved activation pattern induced by MPEP in the young vs. adult brain especially in brain areas regulating stress and circadian rhythms and may be of importance regarding the effect of mGluR5 antagonists in the treatment of mood disorders during juvenile development.

Key words

glutamate - hypothalamus - anxiety - circadian rhythms - puberty
 

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