Cannabinoid Modulation of Midbrain Urocortin 1 Neurones During Acute and Chronic Stress

N. M. Derks, O. Pintér, W. Zuure, C. Ledent, M. Watanabe, C. S. Molnár, Y. Wei, E. W. Roubos, S. Wu, E. Hrabovszky, D. Zelena, T. Kozicz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Neurones in the centrally projecting Edinger-Westphal nucleus (EWcp) are the main site of urocortin 1 (Ucn1) synthesis in the mammalian brain, and are assumed to play a role in the stress response of the animal. Because endocannabinoid signalling has also been strongly implicated in stress, we hypothesised that endocannabinoids may modulate the functioning of the urocortinergic EWcp. First, using in situ hybridisation, we demonstrated cannabinoid receptor 1 (CB1R) mRNA expression in mouse EWcp-neurones that were Ucn1-negative. Dual- and triple-label immunocytochemistry revealed the presence of CB1R in several GABA-immunopositive fibres juxtaposed to EWcp-Ucn1 neurones. To test functional aspects of such an anatomical constellation, we compared acute (1 h of restraint) and chronic (14 days of chronic mild stress) stress-induced changes in wild-type (WT) and CB1R knockout (CB1R-KO) mice. Acute and especially chronic stress resulted in an increase in Ucn1 content of the EWcp, which was attenuated in CB1R-KO mice. CB1R-KO mice had higher basal and chronic stress-induced adrenocorticotrophin and corticosterone levels and were more anxious on the elevated plus-maze versus WT. Collectively, our results show for the first time EWcp-Ucn1 neurones are putatively innervated by endocannabinoid sensitive, inhibitory, GABAergic afferents. In addition, we provide novel evidence that the absence of the CB1 receptor alters the Ucn1 mRNA and peptide levels in EWcp neurones, concomitant with an augmented stress response and increased anxiety-like behaviour.

Original languageEnglish
Pages (from-to)1447-1461
Number of pages15
JournalJournal of Neuroendocrinology
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Urocortins
Cannabinoids
Mesencephalon
Neurons
Endocannabinoids
Knockout Mice
Cannabinoid Receptor CB1
Cannabinoid Receptors
Messenger RNA
Corticosterone
Adrenocorticotropic Hormone
gamma-Aminobutyric Acid
In Situ Hybridization
Anxiety
Immunohistochemistry
Peptides
Brain

Keywords

  • Anxiety
  • Cannabinoid receptor 1-knockout mice
  • Centrally projecting Edinger-Westphal nucleus
  • GABA
  • Midbrain
  • Urocortin 1

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Derks, N. M., Pintér, O., Zuure, W., Ledent, C., Watanabe, M., Molnár, C. S., ... Kozicz, T. (2012). Cannabinoid Modulation of Midbrain Urocortin 1 Neurones During Acute and Chronic Stress. Journal of Neuroendocrinology, 24(11), 1447-1461. https://doi.org/10.1111/j.1365-2826.2012.02355.x

Cannabinoid Modulation of Midbrain Urocortin 1 Neurones During Acute and Chronic Stress. / Derks, N. M.; Pintér, O.; Zuure, W.; Ledent, C.; Watanabe, M.; Molnár, C. S.; Wei, Y.; Roubos, E. W.; Wu, S.; Hrabovszky, E.; Zelena, D.; Kozicz, T.

In: Journal of Neuroendocrinology, Vol. 24, No. 11, 11.2012, p. 1447-1461.

Research output: Contribution to journalArticle

Derks, NM, Pintér, O, Zuure, W, Ledent, C, Watanabe, M, Molnár, CS, Wei, Y, Roubos, EW, Wu, S, Hrabovszky, E, Zelena, D & Kozicz, T 2012, 'Cannabinoid Modulation of Midbrain Urocortin 1 Neurones During Acute and Chronic Stress', Journal of Neuroendocrinology, vol. 24, no. 11, pp. 1447-1461. https://doi.org/10.1111/j.1365-2826.2012.02355.x
Derks, N. M. ; Pintér, O. ; Zuure, W. ; Ledent, C. ; Watanabe, M. ; Molnár, C. S. ; Wei, Y. ; Roubos, E. W. ; Wu, S. ; Hrabovszky, E. ; Zelena, D. ; Kozicz, T. / Cannabinoid Modulation of Midbrain Urocortin 1 Neurones During Acute and Chronic Stress. In: Journal of Neuroendocrinology. 2012 ; Vol. 24, No. 11. pp. 1447-1461.
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