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.
Cannabinoid modulation of alpha(2) adrenergic receptor function in rodent medial prefrontal cortex
Creators
Alessandra M. Cathel - Temple University
Beverly A. S. Reyes - Drexel University
Qin Wang - University of Alabama at Birmingham
Jonathan Palma - Temple University
Kenneth Mackie - Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA
Elisabeth J. Van Bockstaele - Drexel University
Lynn G. Kirby - Temple University
Publication Details
The European journal of neuroscience, v 40(8), pp 3202-3214
Publisher
Wiley
Number of pages
13
Grant note
DA020126; DA020129; DA013429 / NIDA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA)
P30DA013429 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
Resource Type
Journal article
Language
English
Academic Unit
Graduate School - Dean's Office; Pharmacology and Physiology
Web of Science ID
WOS:000344052500007
Scopus ID
2-s2.0-84911448152
Other Identifier
991019184826304721
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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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