Enhanced dendritic availability of μ-opioid receptors in inhibitory neurons of the extended amygdala in mice deficient in the corticotropin-releasing factor-1 receptor.
Activation of the corticotropin-releasing factor-1 (CRF-1) receptor in the anterolateral BNST (BSTal), a key subdivision of the extended amygdala, elicits opiate-seeking behavior exacerbated by stress. However, it is unknown whether the presence of CRF-1 affects expression of the μ-opioid receptor (μ-OR) in the many GABAergic BSTal neurons implicated in the stress response. We hypothesized that deletion of the CRF-1 receptor gene would alter the density and/or subcellular distribution of μ-ORs in GABAergic neurons of the BSTal. We used electron microscopy to quantitatively examine μ-OR immunogold and γ-aminobutyric acid (GABA) immunoperoxidase labeling in the BSTal of CRFr-1 knockout (KO) compared to wild-type (WT) mice. To assess regional specificity, we examined μ-OR distribution in dorsal striatum. The μ-ORs in each region were predominantly localized in dendrites, many of which were GABA-immunoreactive. Significantly, more cytoplasmic μ-OR gold particles per dendritic area were observed selectively in GABA-containing dendrites of the BSTal, but not of the dorsal striatum, in KO compared to WT mice. In both regions, however, significantly fewer GABA-immunoreactive axon terminals were present in KO compared to WT mice. Our results suggest that the absence of CRF-1 results in enhanced expression and/or dendritic trafficking of μ-ORs in inhibitory BSTal neurons. They also suggest that the expression of CRF-1 is a critical determinant of the availability of GABA in functionally diverse brain regions. These findings underscore the complex interplay between CRF, opioid, and GABA systems in limbic and striatal regions and have implications for the role of CRF-1 in influencing the pharmacological effects of opiates active at μ-ORs.
Jaferi
Azra
A
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10065, USA.
Zhou
Ping
P
Pickel
Virginia M
VM
D000679:Amygdala / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D017450:Receptors, Opioid, mu; D005680:gamma-Aminobutyric Acid; D000099052:CRF Receptor, Type 1