Standard water-reinforced drug discrimination model was employed to train Wistar rats to discriminate the intraperitoneal injections of tricyclic antidepressant amitriptyline (5.4 mg/kg) and physiological saline. To examine the role of GABA receptors in psychotropic action of amitriptyline, the substitution tests were performed with muscimol (0.1-1.0 mg/kg) and pregnenolone (30-50 mg/kg). Similar tests were carried out with amitriptyline interoceptive antagonists bicuculline (1 mg/kg), flumazenil (15 mg/kg), finasteride (5 mg/kg), and indomethacin (7.5 mg/kg). The study showed that interoceptive effects of amitriptyline depend on functional activity of GABA receptors but not on the neurosteroid site of GABA receptor complex.
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http://dx.doi.org/10.1007/s10517-020-04704-0 | DOI Listing |
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.
View Article and Find Full Text PDFQ Rev Biophys
January 2025
Faculty of Medicine, Department of Biophysics and Neuroscience, Wroclaw Medical University, Wrocław, Poland.
The GABA type A receptor (GABAR) belongs to the family of pentameric ligand-gated ion channels and plays a key role in inhibition in adult mammalian brains. Dysfunction of this macromolecule may lead to epilepsy, anxiety disorders, autism, depression, and schizophrenia. GABAR is also a target for multiple physiologically and clinically relevant modulators, such as benzodiazepines (BDZs), general anesthetics, and neurosteroids.
View Article and Find Full Text PDFKorean 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 PDFToxicol Lett
January 2025
Bundeswehr Institute for Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany. Electronic address:
The nicotinic acetylcholine receptor (nAChR) is a pentameric ligand-gated ion channel (pLGIC) commonly used as a model for receptors belonging to the Cys-loop superfamily. Members of pLGICs are standardly used in numerous toxicological investigations e.g.
View Article and Find Full Text PDFDrug Res (Stuttg)
January 2025
Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Tolerance to the antinociceptive effects of opioids is a major concern. Studies have shown that chronic use of non-steroidal anti-inflammatory (NSAIDs) causes significant tolerance and cross-tolerance to morphine. Chronic NSAIDs use can increase the risk of certain diseases, such as peptic ulcers, and exacerbate others, like heart failure.
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