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Cannabinoid modulation of alpha(2) adrenergic receptor function in rodent medial prefrontal cortex
Journal article   Open access   Peer reviewed

Cannabinoid modulation of alpha(2) adrenergic receptor function in rodent medial prefrontal cortex

Alessandra M. Cathel, Beverly A. S. Reyes, Qin Wang, Jonathan Palma, Kenneth Mackie, Elisabeth J. Van Bockstaele and Lynn G. Kirby
The European journal of neuroscience, v 40(8), pp 3202-3214
01 Oct 2014
PMID: 25131562
url
https://europepmc.org/articles/pmc4205194View
Accepted (AM)Open Access (License Unspecified) Open

Abstract

Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
Endocannabinoids acting at the cannabinoid type 1 receptor (CB1R) are known to regulate attention, cognition and mood. Previous studies have shown that, in the rat medial prefrontal cortex (mPFC), CB1R agonists increase norepinephrine release, an effect that may be attributed, in part, to CB1Rs localised to noradrenergic axon terminals. The present study was aimed at further characterising functional interactions between CB1R and adrenergic receptor (AR) systems in the mPFC using in vitro intracellular electrophysiology and high-resolution neuroanatomical techniques. Whole-cell patch-clamp recordings of layer V/VI cortical pyramidal neurons in rats revealed that both acute and chronic treatment with the synthetic CB1R agonist WIN 55,212-2 blocked elevations in cortical pyramidal cell excitability and increases in input resistance evoked by the 2-adrenergic receptor (2-AR) agonist clonidine, suggesting a desensitisation of 2-ARs. These CB1R-2-AR interactions were further shown to be both action potential- and gamma-aminobutyric acid-independent. To better define sites of cannabinoid-AR interactions, we localised 2A-adrenergic receptors (2A-ARs) in a genetically modified mouse that expressed a hemoagglutinin (HA) tag downstream of the 2A-AR promoter. Light and electron microscopy indicated that HA-2A-AR was distributed in axon terminals and somatodendritic processes especially in layer V of the mPFC. Triple-labeling immunocytochemistry revealed that 2A-AR and CB1R were localised to processes that contained dopamine--hydroxylase, a marker of norepinephrine. Furthermore, HA-2A-AR was localised to processes that were directly apposed to CB1R. These findings suggest multiple sites of interaction between cortical cannabinoid-adrenergic systems that may contribute to understanding the effect of cannabinoids on executive functions and mood.

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Collaboration types
Domestic collaboration
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Neurosciences
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