Related Experiment Video
Updated: Jun 27, 2026
09:16
A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Secretory vesicle rebound hyperacidification and increased quantal size resulting from prolonged methamphetamine
Dmitriy Markov1, Eugene V Mosharov, Wanda Setlik
1Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Journal of Neurochemistry
|November 19, 2008
Summary
Prolonged exposure to methamphetamine (METH) causes secretory vesicles to become hyperacidified. This compensatory response can enhance catecholamine release, contrary to acute amphetamine (AMPH) effects.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Acute amphetamine (AMPH) exposure disrupts secretory vesicle pH, affecting catecholamine release.
- Methamphetamine (METH) and AMPHs are retained in tissues long-term, suggesting different chronic effects.
Purpose of the Study:
- To investigate the long-term effects of METH on secretory vesicle pH and neurosecretion.
- To determine the impact of chronic METH exposure on catecholamine release from chromaffin cells.
Main Methods:
- Utilized optical and electron microscopy to assess vesicle pH.
- Employed amperometry and intracellular patch electrochemistry to monitor neurosecretion and cytosolic catecholamines.
- Cultured rat chromaffin cells were used to model METH exposure.
Main Results:
- Prolonged METH exposure (6-48h) induced a concentration-dependent rebound hyperacidification of secretory vesicles.
- At 5-10 microM, chronic METH increased quantal size and reinstated exocytotic catecholamine release.
- Rebound hyperacidification was temperature-dependent and occurred with other weak bases, indicating a compensatory mechanism.
Conclusions:
- Chronic METH exposure, unlike acute exposure, can enhance catecholamine release through vesicle hyperacidification.
- This compensatory mechanism is a general response to prolonged exposure to membranophilic weak bases.
- Under specific chronic exposure conditions, AMPHs can enhance rather than deplete vesicular catecholamine release.
Related Concept Videos
01:20Desensitization and Tachyphylaxis
Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...
Several...
01:15Drug Abuse and Addiction: Pharmacological Phenomena
Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not necessarily...
01:23Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
01:33Overview of Secretory Vesicles
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
01:22Drug Elimination by Renal Route: Tubular Reabsorption
During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
01:05Insulin Secretory Vesicles
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...