Purpose: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).
Methods: Male rats were administered PLZ (10 mg/kg) or VIG (1,000 mg/kg) i.p., and the rats were euthanized 4 hours later and the brains removed for analysis of levels of GABA and ALA (by electron capture gas chromatography after derivatization) and activities of MAO, GABA-T and ALA-T (radiochemical assays).
Results: Both PLZ and VIG inhibited GABA-T and elevated GABA levels. Only PLZ inhibited MAO and ALA-T and elevated ALA levels. The effects of PLZ on both amino acids and their transaminases were blocked by pre-treatment with the MAO inhibitor tranylcypromine. This pretreament had no effect on the inhibition of GABA-T or the elevation of brain GABA levels produced by VIG.
Conclusions: At the doses studied, PLZ was as effective as VIG at elevating brain GABA levels, but, unlike VIG, also inhibited MAO and ALA-T (and increased brain ALA levels). Pretreatment of rats with the MAO inhibitor tranylcypromine prevented the increase in brain GABA and ALA levels with PLZ, but did not block the effect of VIG on GABA. These observations with tranylcypromine and PLZ support the hypothesis that an active metabolite of PLZ produced by the actions of MAO on this drug plays a major role in its GABA- and ALA-elevating actions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.18433/j34s38 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
λ-cyhalothrin induced sex-specific inflammation, glia activation and GABAergic interneuron disruption in the hippocampus of rats.
BMC Pharmacol Toxicol
January 2025
Department of Anatomy, College of Health Sciences, University of Ilorin, Ilorin, 240003, Nigeria.
Background: Glia mediated neuroinflammation and degeneration of inhibitory GABAergic interneurons are some of the hall marks of pyrethroid neurotoxicity. Here we investigated the sex specific responses of inflammatory cytokines, microglia, astrocyte and parvalbumin positive inhibitory GABAergic interneurons to λ-cyhalothrin (LCT) exposures in rats.
Methods: Equal numbers of male and female rats were given oral corn oil, 2 mg/kg.
Synthesis and Evaluation of Benzylic F-Labeled -Biphenylalkynyl Nipecotic Acid Derivatives for PET Imaging of GABA Transporter 1.
ACS Chem Neurosci
January 2025
Sensor Engineering Department, Faculty of Science and Engineering, Maastricht University, 6200 MD Maastricht, The Netherlands.
As the main inhibitory neurotransmission system, the GABAergic system poses an interesting yet underutilized target for molecular brain imaging. While PET imaging of postsynaptic GABAergic neurons has been accomplished using radiolabeled benzodiazepines targeting the GABA receptor, the development of presynaptic radioligands targeting GABA transporter 1 (GAT1) has been unsuccessful thus far. Therefore, we developed a novel GAT1-addressing radioligand and investigated its applicability as a PET tracer in rodents.
View Article and Find Full Text PDFMorphological and functional decline of the SNc in a model of progressive parkinsonism.
NPJ Parkinsons Dis
January 2025
Vollum Institute, Oregon Health & Science University, Portland, OR, USA.
The motor symptoms of Parkinson's Disease are attributed to the degeneration of dopamine neurons in the substantia nigra pars compacta (SNc). Previous work in the MCI-Park mouse model has suggested that the loss of somatodendritic dopamine transmission predicts the development of motor deficits. In the current study, brain slices from MCI-Park mice were used to investigate dopamine signaling in the SNc prior to and through the onset of movement deficits.
View Article and Find Full Text PDFTargeting of retrovirus-derived / causes late-onset obesity, reduced social response and increased apathy-like behaviour.
Open 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 PDFGrowth of the prefrontal cortical glioblastoma altered cognitive and emotional behaviors via mediating miRNAs and GABA-A receptor signaling pathways in rats.
Brain Res Bull
January 2025
Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
The present study investigated the impact of GABAergic signaling and miRNA expression on glioblastoma multiforme (GBM) growth within the medial prefrontal cortex (mPFC) and its associated cognitive and emotional impairments. The implantation of C6 cells into the mPFC induced GBM in this brain region (referred to as the mPFC-GBM) in male Wistar rats via stereotaxic surgery, as confirmed by Magnetic Resonance Imaging (MRI), and Hematoxylin and Eosin (H&E) staining. Repeated microinjections of muscimol, a potent GABA receptor agonist, directly into the mPFC-GBM (1 µg/rat/2.
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!