A5007169111- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Neuropeptides and Animal Physiology
- Neuroendocrine regulation and behavior
- Adipose Tissue and Metabolism
- Nicotinic Acetylcholine Receptors Study
- HIV Research and Treatment
- Regulation of Appetite and Obesity
- Diet and metabolism studies
- Attention Deficit Hyperactivity Disorder
- Tryptophan and brain disorders
- SARS-CoV-2 and COVID-19 Research
- Memory and Neural Mechanisms
- Pain Mechanisms and Treatments
- Pharmacological Receptor Mechanisms and Effects
- Neural dynamics and brain function
- Electrochemical Analysis and Applications
- Photoreceptor and optogenetics research
- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Parkinson's Disease Mechanisms and Treatments
- Sleep and related disorders
Wake Forest University
2016-2025
Rajiv Gandhi Centre for Biotechnology
2017-2024
Institute of Virology of the Slovak Academy of Sciences
2024
All India Institute of Medical Sciences Bhubaneswar
2024
King George's Medical University
2024
Parkland Health & Hospital System
2023
Prisma Health
2022
Leidos (United States)
2014-2020
Frederick National Laboratory for Cancer Research
2018-2020
Cardiff and Vale University Health Board
2020
The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic is currently unknown. Mice lacking the gene encoding plasma membrane dopamine transporter (DAT) have elevated dopaminergic tone and are hyperactive. This activity was exacerbated exposure to a novel environment. Additionally, these mice were impaired spatial cognitive function, they showed decrease locomotion response psychostimulants. paradoxical...
The dopamine transporter (DAT) plays an important role in calibrating the duration and intensity of neurotransmission central nervous system. We have used a strain mice which gene for DAT has been genetically deleted to identify DAT’s homeostatic role. find that removal dramatically prolongs lifetime (300 times) extracellular dopamine. Within time frame neurotransmission, no other processes besides diffusion can compensate lack DAT, absence produces extensive adaptive changes control...
Amphetamine (AMPH) inhibits uptake and causes release of dopamine (DA) from presynaptic terminals. AMPH can act on both vesicular storage DA directly the transporter (DAT). To assess relative importance these two processes, we have examined releasing actions in mice with a genetic deletion DAT. The sequence has been determined by following real time changes extracellular fluid intact tissue fast scan cyclic voltammetry. In striatal slices wild-type mice, gradual (∼30 min) increase DA,...
Abnormal dopaminergic transmission is implicated in schizophrenia, attention deficit hyperactivity disorder, and drug addiction. In an attempt to model aspects of these disorders, we have generated hyperdopaminergic mutant mice by reducing expression the dopamine transporter (DAT) 10% wild-type levels (DAT knockdown). Fast-scan cyclic voltammetry vivo microdialysis revealed that released was cleared at a slow rate knockdown mice, which resulted higher extracellular concentration. Unlike DAT...
Abstract The type-V CRISPR effector Cas12b (formerly known as C2c1) has been challenging to develop for genome editing in human cells, at least part due the high temperature requirement of characterized family members. Here we explore diversity and identify a promising candidate gene from Bacillus hisashii , BhCas12b. However, 37 °C, wild-type BhCas12b preferentially nicks non-target DNA strand instead forming double break, leading lower efficiency. Using combination approaches,...
Agonists targeting the kappa opioid receptor (KOR) have been promising therapeutic candidates because of their efficacy for treating intractable itch and relieving pain. Unlike typical narcotics, KOR agonists do not produce euphoria or lead to respiratory suppression overdose. However, they dysphoria sedation, side effects that precluded clinical development as therapeutics. signaling can be fine-tuned preferentially activate certain pathways over others, such bias so signals through G...
The neurotoxic effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was tested on mice lacking the dopamine (DA) transporter (DAT-/- mice). Striatal tissue DA content and glial fibrillary acidic protein (GFAP) mRNA expression were assessed as markers MPTP neurotoxicity. (30 mg/kg, s.c., b.i.d.) produced an 87% decrease in levels a 29-fold increase level GFAP striatum wild-type animals 48 h after administration. Conversely, there no significant changes either parameter DAT-/- mice....
Abstract Recent evidence suggests that the hypocretin–orexin system participates in regulation of reinforcement processes. The current studies examined extent to which hypocretin neurotransmission regulates behavioral and neurochemical responses cocaine, food reinforcement. These used a combination fixed ratio, discrete trials, progressive ratio threshold self‐administration procedures assess whether 1 receptor antagonist, SB‐334867, reduces cocaine rats. Progressive sucrose were also...
Mutations in the DJ-1 gene were recently identified an autosomal recessive form of early-onset familial Parkinson disease. Structural biology, biochemistry, and cell biology studies have suggested potential functions oxidative stress, protein folding, degradation pathways. However, animal models are needed to determine whether how loss function leads We generated null mice with a mutation that resembles large deletion reported patients. Our behavioral analyses indicated deficiency led...
Regional differences in the kinetics and pharmacological inhibition of dopamine uptake were investigated with fast-scan cyclic voltammetry both intact rat brain a slice preparation. The regions compared basolateral amygdaloid nucleus, caudate-putamen, nucleus accumbens. frequency dependence efflux evoked vivo by electrical stimulation medial forebrain bundle was evaluated nonlinear curve fitting Michaelis-Menten-based kinetic model. Km for found to be significantly higher amygdala (0.6...
The majority of neurotransmitter systems shows variations in state-dependent cell firing rates that are mechanistically linked to extracellular levels, or tone, their respective neurotransmitter. Diurnal variation dopamine tone has also been demonstrated within the striatum, but this is unique, likely not related firing; largely because observation midbrain neurons do display diurnal fluctuations rates. Therefore, we conducted a systematic investigation possible mechanisms for tone. Using...
Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to negative affective symptoms associated with withdrawal. Kappa opioid receptors have been implicated withdrawal-induced excessive drinking and anxiety-like behaviors are known inhibit release accumbens. The effects of chronic on kappa receptor-mediated changes at level terminal withdrawal-related were examined. Five weeks intermittent male C57BL/6 mice used examine role ethanol-induced...