scholarly journals Development of an MRI-Compatible Nasal Drug Delivery Method for Probing Nicotine Addiction Dynamics

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2069
Author(s):  
Rajat Kumar ◽  
Lilianne R. Mujica-Parodi ◽  
Michael Wenke ◽  
Anar Amgalan ◽  
Andrew Lithen ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Nicotine Addiction ◽  
Fixed Interval ◽  
Nasal Delivery ◽  
Single Subject ◽  
Delivery Method ◽  
Nasal Drug Delivery ◽  
Self Administration ◽  
Nicotine Delivery ◽  
Magnetic Resonance Imaging Mri

Substance abuse is a fundamentally dynamic disease, characterized by repeated oscillation between craving, drug self-administration, reward, and satiety. To model nicotine addiction as a control system, a magnetic resonance imaging (MRI)-compatible nicotine delivery system is needed to elicit cyclical cravings. Using a concentric nebulizer, inserted into one nostril, we delivered each dose equivalent to a single cigarette puff by a syringe pump. A control mechanism permits dual modes: one delivers puffs on a fixed interval programmed by researchers; with the other, subjects press a button to self-administer each nicotine dose. We tested the viability of this delivery method for studying the brain’s response to nicotine addiction in three steps. First, we established the pharmacokinetics of nicotine delivery, using a dosing scheme designed to gradually achieve saturation. Second, we lengthened the time between microdoses to elicit craving cycles, using both fixed-interval and subject-driven behavior. Finally, we demonstrate a potential application of our device by showing that a fixed-interval protocol can reliably identify neuromodulatory targets for pharmacotherapy or brain stimulation. Our MRI-compatible nasal delivery method enables the measurement of neural circuit responses to drug doses on a single-subject level, allowing the development of data-driven predictive models to quantify individual dysregulations of the reward control circuit causing addiction.

scholarly journals Development of an MRI Compatible Nasal Drug Delivery Method: Probing Nicotine Addiction Dynamics

2020 ◽  
Author(s):  
Lilianne R. Mujica-Parodi ◽  
Rajat Kumar ◽  
Michael Wenke ◽  
Anar Amgalan ◽  
Andrew Lithen ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Nicotine Addiction ◽  
Fixed Interval ◽  
Nasal Delivery ◽  
Single Subject ◽  
Delivery Method ◽  
Nasal Drug Delivery ◽  
Self Administration ◽  
Nicotine Delivery ◽  
Drug Doses

AbstractBackgroundSubstance abuse is a fundamentally dynamic disease, characterized by repeated oscillation between craving, drug self-administration, reward, and satiety. To model nicotine addiction as a control system, an MR-compatible nicotine delivery system is needed to elicit cyclical cravings.MethodUsing a concentric nebulizer, inserted into one nostril, we delivered each dose—each equivalent to a single cigarette puff—using a syringe pump by nebulizing the nicotine solution using pressurized medical air. A control mechanism permits dual modes: one delivers puffs on a fixed interval programmed by researchers; with the other, subjects press a button to self-administer each nicotine dose. Subjects were therefore able to intuitively “smoke” the equivalent of a cigarette, one “puff” at a time. We dosed each “puff” such that one cigarette would be equal, in nicotine content, to 10 puffs.ResultsWe tested the viability of this delivery method for studying the brain’s response to nicotine addiction in three steps. First, we established the pharmacokinetics of nicotine delivery, using a dosing scheme designed to gradually achieve saturation, as with a cigarette. Second, we lengthened the time between micro-doses to elicit craving cycles, using both fixed-interval and subject-driven behavior. Finally, we confirmed that the fixed-interval protocol reliably activates brain circuits linked to addiction.ConclusionOur MR-compatible nasal delivery method enables the measurement of neural circuit responses to drug doses on a single-subject level, allowing the development of data-driven predictive models to quantify individual dysregulations of the reward control circuit causing addiction.

scholarly journals A detailed analysis of anatomical plausibility of crossed and uncrossed streamline rendition of the dentato-rubro-thalamic tract (DRT(T)) in a commercial stereotactic planning system

2021 ◽  
Author(s):  
Volker A. Coenen ◽  
Bastian E. Sajonz ◽  
Peter C. Reinacher ◽  
Christoph P. Kaller ◽  
Horst Urbach ◽  
...  
Keyword(s):  
Surgical Planning ◽  
Ground Truth ◽  
Planning System ◽  
Single Subject ◽  
Fiber Structure ◽  
Native Space ◽  
Volume Of Interest ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual

Abstract Background An increasing number of neurosurgeons use display of the dentato-rubro-thalamic tract (DRT) based on diffusion weighted imaging (dMRI) as basis for their routine planning of stimulation or lesioning approaches in stereotactic tremor surgery. An evaluation of the anatomical validity of the display of the DRT with respect to modern stereotactic planning systems and across different tracking environments has not been performed. Methods Distinct dMRI and anatomical magnetic resonance imaging (MRI) data of high and low quality from 9 subjects were used. Six subjects had repeated MRI scans and therefore entered the analysis twice. Standardized DICOM structure templates for volume of interest definition were applied in native space for all investigations. For tracking BrainLab Elements (BrainLab, Munich, Germany), two tensor deterministic tracking (FT2), MRtrix IFOD2 (https://www.mrtrix.org), and a global tracking (GT) approach were used to compare the display of the uncrossed (DRTu) and crossed (DRTx) fiber structure after transformation into MNI space. The resulting streamlines were investigated for congruence, reproducibility, anatomical validity, and penetration of anatomical way point structures. Results In general, the DRTu can be depicted with good quality (as judged by waypoints). FT2 (surgical) and GT (neuroscientific) show high congruence. While GT shows partly reproducible results for DRTx, the crossed pathway cannot be reliably reconstructed with the other (iFOD2 and FT2) algorithms. Conclusion Since a direct anatomical comparison is difficult in the individual subjects, we chose a comparison with two research tracking environments as the best possible “ground truth.” FT2 is useful especially because of its manual editing possibilities of cutting erroneous fibers on the single subject level. An uncertainty of 2 mm as mean displacement of DRTu is expectable and should be respected when using this approach for surgical planning. Tractographic renditions of the DRTx on the single subject level seem to be still illusive.

scholarly journals Disruption of VGLUT1 in cholinergic medial habenula projections increases nicotine self-administration

2021 ◽  
Author(s):  
Elizabeth A Souter ◽  
Yen-Chu Chen ◽  
Vivien Zell ◽  
Valeria Lallai ◽  
Thomas Steinkellner ◽  
...  
Keyword(s):  
Cholinergic Neurons ◽  
Nicotine Addiction ◽  
Conditional Knockout ◽  
Self Administration ◽  
Interpeduncular Nucleus ◽  
Medial Habenula ◽  
Field Assay ◽  
Nicotine Consumption ◽  
Additional Support ◽  
Cholinergic Projections

Cholinergic projections from the medial habenula (MHb) to the interpeduncular nucleus (IPN) have been studied for their complex contributions to nicotine addiction and have been implicated in nicotine reinforcement, aversion, and withdrawal. While it has been established that MHb cholinergic projections co-release glutamate, no direct evidence has demonstrated a role for this specific glutamate projection in nicotine consumption. In the present study, a novel floxed Slc17a7 (VGLUT1) mouse was generated and used to create conditional knockout (cKO) mice that lack VGLUT1 in MHb cholinergic neurons. Histochemical approaches and optogenetics-assisted electrophysiology were used to validate the disruption of VGLUT1 from cholinergic MHb to IPN projections. The mice displayed no gross phenotypic abnormalities and exhibited normal exploratory and locomotor behavior in the open-field assay. However, the loss of VGLUT1-mediated glutamate co-release led to increased nicotine self-administration. These findings indicate that glutamate co-release from ventral MHb cholinergic neurons opposes nicotine consumption and provide additional support for targeting this synapse to develop potential treatments to nicotine addiction.

A Method for Illustrating the Continuity of Behavior during Schedules of Reinforcement

2000 ◽  
Vol 27 (2) ◽  
pp. 145-148 ◽  
Author(s):  
Francisco J. Silva ◽  
Ruhiyyih Yuille ◽  
Lisa K. Peters
Keyword(s):  
Operant Behavior ◽  
Fixed Ratio ◽  
Fixed Interval ◽  
Single Subject ◽  
Schedules Of Reinforcement ◽  
Computer Screen ◽  
Assignment Of Credit ◽  
First Contact

In this article, we present a method for illustrating the continuity of behavior during schedules of reinforcement. Students experienced either a fixed-interval 15-sec schedule in which the first contact after 15 sec of a cursor on a computer screen with a 0.7-cm diameter virtual (invisible) target resulted in reinforcement (a beep) or a fixed-ratio 5 schedule in which every 5th contact with the target produced the reinforcer. In addition to illustrating the continuity of behavior, this method provides a means of exposing students to concepts and methods such as the acquisition of operant behavior, the assignment-of-credit problem, the organization of behavior across time, and the analysis of single-subject data.

scholarly journals A REVIEW ON NASAL DRUG DELIVERY SYSTEM AND ITS CONTRIBUTION IN THERAPEUTIC MANAGEMENT

2019 ◽  
Vol 12 (1) ◽  
pp. 40
Author(s):  
Sulaiman Alnasser
Keyword(s):  
Drug Delivery ◽  
Nasal Cavity ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Absorption ◽  
Delivery Systems ◽  
Nasal Delivery ◽  
Present Review ◽  
Drug Formulations ◽  
Nasal Drug Delivery

Nasal drug delivery has received a great deal of attention as a convenient, reliable, and promising method for the systemic administration of drugs. It is especially for those molecules which are ineffective orally and only effective if administered by injection. The nasal route of drug delivery has advantages over the other alternative systems of non-invasive drug administration. The present review describes nasal delivery systems in recognizing to its potential and limits. The present review is an attempt to provide some information concerning nasal drug delivery system such as limitations, advantages, mechanism of drug absorption, anatomy of nasal cavity, factors affecting of nasal drug delivery, strategies to enhance nasal absorption, strategies to extend duration of drug formulations within the nasal cavity, leading to improved nasal drug absorption, novel drug formulations, sorts of nasal drug delivery system with uses of nasal drug delivery in various diseases, and recent advancement of nasal delivery systems.

scholarly journals Silent myelin-weighted magnetic resonance imaging

2020 ◽  
Vol 5 ◽  
pp. 74
Author(s):  
Tobias C. Wood ◽  
Nikou L. Damestani ◽  
Andrew J. Lawrence ◽  
Emil Ljungberg ◽  
Gareth J. Barker ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Magnetization Transfer ◽  
Patient Comfort ◽  
Head Orientation ◽  
Single Subject ◽  
Resonance Imaging ◽  
Subject Positioning ◽  
Magnetic Resonance Imaging Mri ◽  
Silent Mri

Background: Inhomogeneous Magnetization Transfer (ihMT) is an emerging, uniquely myelin-specific magnetic resonance imaging (MRI) contrast. Current ihMT acquisitions utilise fast Gradient Echo sequences which are among the most acoustically noisy MRI sequences, reducing patient comfort during acquisition. We sought to address this by modifying a near silent MRI sequence to include ihMT contrast. Methods: A Magnetization Transfer preparation module was incorporated into a radial Zero Echo-Time sequence. Repeatability of the ihMT ratio and inverse ihMT ratio were assessed in a cohort of healthy subjects. We also investigated how head orientation affects ihMT across subjects, as a previous study in a single subject suggests this as a potential confound. Results: We demonstrated that ihMT ratios comparable to existing, acoustically loud, implementations could be obtained with the silent sequence. We observed that the ihMT ratio varied with the orientation of the head. Conclusions: Silent ihMT imaging is a comparable alternative to conventional, noisy, alternatives. For all future ihMT studies we recommend careful attention should be paid to subject positioning within the scanner.

scholarly journals Silent myelin-weighted magnetic resonance imaging

2020 ◽  
Vol 5 ◽  
pp. 74
Author(s):  
Tobias C. Wood ◽  
Nikou L. Damestani ◽  
Andrew J. Lawrence ◽  
Emil Ljungberg ◽  
Gareth J. Barker ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Magnetization Transfer ◽  
Patient Comfort ◽  
Head Orientation ◽  
Single Subject ◽  
Resonance Imaging ◽  
Mri Contrast ◽  
Magnetic Resonance Imaging Mri ◽  
Silent Mri

Background: Inhomogeneous Magnetization Transfer (ihMT) is an emerging, uniquely myelin-specific magnetic resonance imaging (MRI) contrast. Current ihMT acquisitions utilise fast Gradient Echo sequences which are among the most acoustically noisy MRI sequences, reducing patient comfort during acquisition. We sought to address this by modifying a near silent MRI sequence to include ihMT contrast. Methods: A Magnetization Transfer preparation module was incorporated into a radial Zero Echo-Time sequence. Repeatability of the ihMT ratio and inverse ihMT ratio were assessed in a cohort of healthy subjects. We also investigated how head orientation affects ihMT across subjects, as a previous study in a single subject suggests this as a potential confound. Results: We demonstrated that ihMT ratios comparable to existing, acoustically loud, implementations could be obtained with the silent sequence. We observed a small but significant effect of head orientation on inverse ihMTR. Conclusions: Silent ihMT imaging is a comparable alternative to conventional, noisy, alternatives. For all future ihMT studies we recommend careful positioning of the subject within the scanner.

scholarly journals The Application of Mucoadhesive Chitosan Nanoparticles in Nasal Drug Delivery

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 605
Author(s):  
Soojin Shim ◽  
Han Sang Yoo
Keyword(s):  
Nasal Cavity ◽  
Chitosan Nanoparticles ◽  
Drug Efficacy ◽  
Mucosal Immune Response ◽  
Delivery Systems ◽  
Nasal Delivery ◽  
Antigen Delivery ◽  
Nasal Drug Delivery ◽  
Administration Routes ◽  
Cellular Immune

Mucosal delivery of antigens can induce both humoral and cellular immune responses. Particularly, the nasal cavity is a strongly inductive site for mucosal immunity among several administration routes, as it is generally the first point of contact for inhaled antigens. However, the delivery of antigens to the nasal cavity has some disadvantages such as rapid clearance and disposition of inhaled materials. For these reasons, remarkable efforts have been made to develop antigen delivery systems which suit the nasal route. The use of nanoparticles as delivery vehicles enables protection of the antigen from degradation and sustains the release of the loaded antigen, eventually resulting in improved vaccine and/or drug efficacy. Chitosan, which exhibits low toxicity, biodegradability, good cost performance, and strong mucoadhesive properties, is a useful material for nanoparticles. The present review provides an overview of the mucosal immune response induced by nanoparticles, recent advances in the use of nanoparticles, and nasal delivery systems with chitosan nanoparticles.

Electronic nicotine delivery systems, adolescent use, and nicotine addiction

2019 ◽  
Vol 44 (11) ◽  
pp. 10-13
Author(s):  
Debra Vincent ◽  
Jeanne Potts ◽  
Jessica Durbin ◽  
Jill Moore ◽  
Susan Eley
Keyword(s):  
Delivery Systems ◽  
Nicotine Addiction ◽  
Electronic Nicotine Delivery Systems ◽  
Nicotine Delivery

Road From Nose to Brain for Treatment of Alzheimer: The Bumps and Humps

2020 ◽  
Vol 19 (9) ◽  
pp. 663-675
Author(s):  
Rajesh Kumar ◽  
Monica Gulati ◽  
Sachin Kumar Singh ◽  
Deepika Sharma ◽  
Omji Porwal
Keyword(s):  
Drug Delivery ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Nasal Delivery ◽  
Brain Barrier ◽  
Nasal Drug Delivery ◽  
Blood Brain ◽  
Routes Of Drug Administration ◽  
Alternative Routes ◽  
The Brain

: Vulnerability of the brain milieu to even the subtle changes in its normal physiology is guarded by a highly efficient blood brain barrier. A number of factors i.e. molecular weight of the drug, its route of administration, lipophilic character etc. play a significant role in its sojourn through the blood brain barrier (BBB) and limit the movement of drug into brain tissue through BBB. To overcome these problems, alternative routes of drug administration have been explored to target the drugs to brain tissue. Nasal route has been widely reported for the administration of drugs for treatment of Alzheimer. In this innovative approach, the challenge of BBB is bypassed. Through this route, both the larger as well as polar molecules can be made to reach the brain tissues. Generally, these systems are either pH dependent or temperature dependent. Results: The present review highlights the anatomy of nose, mechanisms of drug delivery from nose to brain, critical factors in the formulation of nasal drug delivery system, nasal formulations of various drugs that have been tried for their nasal delivery for treatment of Alzheimer. Conclusion: It also dives deep to understand the factors that contribute to the success of such formulations to carve out a direction for this niche area to be explored further.

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