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Background: Despite increasing fatal stimulant poisoning in the United States, little is understood about the mechanism of death. The psychological autopsy (PA) has long been used to distinguish the manner of death in equivocal cases, including opioid overdose, but has not been used to explicitly explore stimulant mortality.

Objective: We aimed to develop and implement a large PA study to identify antecedents of fatal stimulant poisoning, seeking to maximize data gathering and ethical interactions during the collateral interviews.

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3,4-methylenedioxymethamphetamine (MDMA; commonly referred to as "ecstasy" or "molly") is a substituted amphetamine drug that is used recreationally for its acute psychoactive effects, including euphoria and increased energy, as well as prosocial effects such as increased empathy and feelings of closeness with others. Acute adverse effects can include hyperthermia, dehydration, bruxism, and diaphoresis. Post-intoxication phenomena may include insomnia, anhedonia, anxiety, depression, and memory impairment, which can persist for days following drug cessation.

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Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity.

Neurotox Res

January 2025

Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA, 21224, Baltimore, MD, U.S.A.

To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.

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Investigating intrauterine exposure to methamphetamine on serine-threonine kinase pathway in male rat testis.

Cell Mol Biol (Noisy-le-grand)

January 2025

Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Article Synopsis
  • Intrauterine exposure to methamphetamine (METH) during pregnancy negatively impacts testicular development in offspring, leading to apoptosis in spermatids.
  • Research focused on proteins involved in sperm growth pathways, particularly TSSK and RIPK2, showing significant changes in their expression levels due to METH exposure.
  • Findings indicated that METH exposure resulted in decreased TSSK expression, increased RIPK2 expression, thinner germ layers, more inflammatory cells, and a reduction in the thickness of seminiferous tubules in rat testes.
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The ventromedial prefrontal cortex (VMPFC), located along the medial aspect of the frontal area, plays a critical role in regulating arousal/emotions. Its intricate connections with subcortical structures, including the striatum and amygdala, highlight the VMPFC's importance in the neurocircuitry of addiction. Due to these features, the VMPFC is considered a promising target for transcranial magnetic stimulation (TMS) in substance use disorders (SUD).

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