sigma(1) Receptors have been implicated in the modulation of opioid analgesia. In the current study, we examined the role of sigma(1) systems in the periaqueductal gray (PAG), the rostroventral medulla (RVM), and the locus coeruleus (LC) of the rat, regions previously shown to be sensitive to morphine. Morphine was a potent analgesic in all three regions. Coadministration of the sigma(1) agonist (+)-pentazocine diminished the analgesic actions of morphine in all three regions, although the PAG was far less sensitive than the other two regions. Blockade of the sigma(1) receptors with haloperidol in the RVM markedly enhanced the analgesic actions of coadministered morphine, implying a tonic activity of the sigma(1) system in this region. This effect was mimicked by down-regulation of RVM sigma(1) receptors using an antisense approach. However, no tonic sigma(1) activity was observed in either the LC or the PAG. The RVM also was important in modulating analgesia elicited from morphine microinjected into the PAG. The analgesic actions of morphine given into the PAG could be attenuated by (+)-pentazocine placed into the RVM, whereas haloperidol in the RVM enhanced PAG morphine analgesia. These studies illustrate the pharmacological importance of sigma(1) receptors in the brainstem modulation of opioid analgesia.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1124/jpet.107.121137 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.
Cancer Biol Ther
December 2025
Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER.
View Article and Find Full Text PDFSigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons.
Biomolecules
January 2025
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, China.
The sigma-1 receptor (Sig-1R) has emerged as a significant target in the realm of pain management and has been the subject of extensive research. Nonetheless, its specific function in inflammatory pain within dorsal root ganglion (DRG) neurons remains inadequately elucidated. This study utilized whole-cell patch clamp techniques, single-cell real-time PCR, and immunohistochemistry to examine the influence of Sig-1R on inflammatory pain induced by complete Freund's adjuvant (CFA) in a rat model.
View Article and Find Full Text PDFAfobazole alleviates streptozotocin-induced diabetic nephropathy in rats via hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties: Role of the S1R/Nrf2 antioxidant axis.
Life Sci
January 2025
Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Aims: Sigma-1 receptor (S1R) activation was recently identified as a promising target for preventing diabetic nephropathy (DN) by mitigating hypoxia, oxidative stress, and inflammation. This study aimed to investigate the potential reno-protective effect of the S1R agonist afobazole against streptozotocin (STZ)-induced DN in rats compared to metformin.
Materials And Methods: Rats were split into six groups: the normal control group; the diabetic control group received STZ (55 mg/kg i.
N, N-dimethyltryptamine (DMT) in rodent brain: Concentrations, distribution, and recent pharmacological data.
Prog Neuropsychopharmacol Biol Psychiatry
January 2025
Louisiana State University, Department of Comparative Biomedical Sciences, Baton Rouge, LA 70803, United States of America. Electronic address:
Renewed interest in the clinical use of psychedelic drugs acknowledges their therapeutic effectiveness. It has also provided a changing frame of reference for older psychedelic drug study data, especially regarding concentrations of N, N-dimethyltryptamine (DMT) reported in rodent brains and recent discoveries in DMT receptor interactions in rat brain neurons and select brain areas. The mode of action of DMT in its newly defined role as a neuroplastogen, its effectiveness in treating neuropsychiatric disorders, and its binding to intracellular sigma-1 and 5HT2a receptors may define these possible roles.
View Article and Find Full Text PDFNeurosteroids and neurological disorders.
Korean J Physiol Pharmacol
January 2025
Department of Pharmacology, Catholic Kwandong University College of Medicine, Gangneung 25601, Korea.
Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl- D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!