The neurosteroid, 5α-pregnan-3α-ol-20-one (known as "allopregnanolone" or 3α,5α-THP), is produced in the midbrain ventral tegmental area (VTA), independent of peripheral sources of progestogens, where it has potential actions at N-methyl-D-aspartate (NMDA) and GABA receptors to facilitate rodent sexual behavior. Progestogens can also have anti-anxiety effects, but whether these involve actions of centrally-derived 3α,5α-THP or these receptors to support reproductively-relevant behavior is not well understood. We investigated the extent to which 3α,5α-THP's actions NMDA and/or GABA receptors in the midbrain VTA influence reproductive behaviors. Estradiol-primed, ovariectomized/adrenalectomized (OVX/ADX) rats received midbrain VTA infusions of vehicle, an NMDA receptor blocker (MK-801; 200 ng), or a GABA receptor blocker (bicuculline; 100 ng) followed by a second infusion of vehicle or 3α,5α-THP (100 ng). Reproductively-relevant behaviors were assessed: sexual (paced mating), anxiety-like (elevated plus maze), and social (partner preference, social interaction) behavior. Compared to vehicle, intra-VTA infusions of MK-801 exerted anxiolytic-like effects on elevated plus maze behavior and enhanced lordosis. Unlike prior observations in gonadally-intact rats, intra-VTA bicuculline had no effect on the behavior of OVX/ADX rats (likely due to a floor effect). Subsequent infusions of 3α,5α-THP reversed effects on lordosis and infusions of bicuculline inhibited 3α,5α-THP-facilitated lordosis. Thus, NMDA and GABA receptors may act as mediators for reproductive behavioral effects of 3α,5α-THP in the midbrain VTA.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026732 | PMC |
http://dx.doi.org/10.3389/fnbeh.2020.00011 | DOI Listing |
Front Pharmacol
January 2025
Laboratory of Traditional Chinese Medicine and Stress Injury of Shandong Province, Laboratory Animal Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
Introduction: Premenstrual dysphoric disorder (PMDD) is a cyclical mood disorder that severely affects the daily life of women of reproductive age. Most of the medications being used clinically have limitations such as low efficacy, side effects, and high cost, so there is an urgent need to discover safer and more effective medications. Rutin is a natural flavonol glycoside with various pharmacological properties including antidepressant.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Neurology, Huashan Hospital, Fudan University and Institute of Neurology, Fudan University, Shanghai, China.
We report a case of optic neuritis (ON) secondary to autoimmune encephalitis (AE) in a patient with concomitant antibodies to N-methyl-D-aspartate receptor (NMDAR), gamma-aminobutyric acid-B receptor (GABAR), and myelin oligodendrocyte glycoprotein (MOG). The patient exhibited a constellation of symptoms, including vision loss, seizures, mental and behavioral disorders, cognitive impairment, and speech abnormalities. At the two-year follow-up, the patient's symptoms had abated entirely.
View Article and Find Full Text PDFOpen Biol
January 2025
Department of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Retrotransposon Gag-like (RTL) 8A, 8B and 8C are eutherian-specific genes derived from a certain retrovirus. They cluster as a triplet of genes on the X chromosome, but their function remains unknown. Here, we demonstrate that and play important roles in the brain: their double knockout (DKO) mice not only exhibit reduced social responses and increased apathy-like behaviour, but also become obese from young adulthood, similar to patients with late Prader-Willi syndrome (PWS), a neurodevelopmental genomic imprinting disorder.
View Article and Find Full Text PDFEur J Med Chem
January 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, Xicheng district, Beijing, 100050, China. Electronic address:
A novel class of 7-phenyl-[1,2,4]triazol-5(4H)-one derivatives was designed and synthesized, and their in vivo anticonvulsant activities were evaluated using subcutaneous pentylenetetrazole (Sc-PTZ) and maximal electroshock (MES) tests. Compounds 3u, 4f and 4k exhibited significant anticonvulsant activities in the Sc-PTZ model with ED values of 23.7, 17.
View Article and Find Full Text PDFJ Neurochem
January 2025
School of Life Science, Nanchang University, Nanchang, China.
Activation of the brain-penetrant beta3-adrenergic receptor (Adrb3) is implicated in the treatment of depressive disorders. Enhancing GABAergic inputs from interneurons onto pyramidal cells of prefrontal cortex (PFC) represents a strategy for antidepressant therapies. Here, we probed the effects of the activation of Adrb3 on GABAergic transmission onto pyramidal neurons in the PFC using in vitro electrophysiology.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!