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Journal article
Co-localization of the cannabinoid type 1 receptor with corticotropin-releasing factor-containing afferents in the noradrenergic nucleus locus coeruleus: implications for the cognitive limb of the stress response
Brain structure & function, v 222(7), pp 3007-3023
Sep 2017
PMID: 28255675
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The noradrenergic system has been shown to play a key role in the regulation of stress responses, arousal, mood, and emotional states. Corticotropin-releasing factor (CRF) is a primary mediator of stress-induced activation of noradrenergic neurons in the nucleus locus coeruleus (LC). The endocannabinoid (eCB) system also plays a key role in modulating stress responses, acting as an "anti-stress" neuro-mediator. In the present study, we investigated the cellular sites for interactions between the cannabinoid receptor type 1 (CB1r) and CRF in the LC. Immunofluorescence and high-resolution immunoelectron microscopy showed co-localization of CB1r and CRF in both the core and peri-LC areas. Semi-quantitative analysis revealed that 44% (208/468) of CRF-containing axon terminals in the core and 35% (104/294) in the peri-LC expressed CB1r, while 18% (85/468) of CRF-containing axon terminals in the core and 6.5% (19/294) in the peri-LC were presynaptic to CB1r-containing dendrites. In the LC core, CB1r + CRF axon terminals were more frequently of the symmetric (inhibitory) type; while in the peri-LC, a majority were of the asymmetric (excitatory) type. Triple label immunofluorescence results supported the ultrastructural analysis indicating that CB1r + CRF axon terminals contained either gamma amino butyric acid or glutamate. Finally, anterograde transport from the central nucleus of the amygdala revealed that CRF-amygdalar afferents projecting to the LC contain CB1r. Taken together, these results indicate that the eCB system is poised to directly modulate stress-integrative heterogeneous CRF afferents in the LC, some of which arise from limbic sources.
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Details
- Title
- Co-localization of the cannabinoid type 1 receptor with corticotropin-releasing factor-containing afferents in the noradrenergic nucleus locus coeruleus: implications for the cognitive limb of the stress response
- Creators
- Ryan R Wyrofsky - Department of Pharmacology and Physiology, College of Medicine, Drexel University, 245 S. 15th Street, Philadelphia, PA, 19102, USA. rrw47@drexel.eduBeverly A S Reyes - Drexel UniversityElisabeth J Van Bockstaele - Drexel University
- Publication Details
- Brain structure & function, v 222(7), pp 3007-3023
- Publisher
- Springer Nature
- Grant note
- DA020129 / National Institute on Drug Abuse
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000409250300005
- Scopus ID
- 2-s2.0-85014111272
- Other Identifier
- 991019184820704721
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- Web of Science research areas
- Anatomy & Morphology
- Neurosciences