Related Experiment Video
Updated: Jul 19, 2026
07:16
Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Methamphetamine induces long-term changes in GABAA receptor alpha2 subunit and GAD67 expression
Xiuwu Zhang1, Tong H Lee, Xueying Xiong
1Department of Psychiatry and Behavioral Science, Duke University Medical Center, Durham, NC 27710, USA. xwzhang@duke.edu
Biochemical and Biophysical Research Communications
|October 24, 2006
Summary
Methamphetamine (METH) sensitization involves changes in GABA(A) receptor alpha2 subunit and GAD(67) levels. These alterations in the nucleus accumbens and caudate are linked to METH
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Chronic high-dose methamphetamine (METH) use can lead to behavioral sensitization and neurotoxicity.
- The roles of GABAergic system components, specifically the GABA(A) receptor alpha2 subunit and GAD(67), in METH-induced effects remain incompletely understood.
Purpose of the Study:
- To investigate the involvement of the GABA(A) receptor alpha2 subunit and GAD(67) in chronic METH-induced sensitization and neurotoxicity.
- To determine the regional changes in these proteins within the nucleus accumbens (NAc) and caudate following METH exposure.
Main Methods:
- METH sensitization was induced in rats via a 7-day pump infusion and daily injections, followed by a 28-day withdrawal period.
- Behavioral sensitization was assessed using behavioral ratings after a METH challenge.
- Neurotoxicity was evaluated by measuring glial fibrillary acidic protein (GFAP) expression using Western blot assays.
Main Results:
- METH sensitization decreased GABA(A) alpha2 subunit and GAD(67) protein levels in the nucleus accumbens core and shell.
- Conversely, these protein levels were increased in the caudate following METH sensitization.
- An upregulation of GFAP expression, a marker of neurotoxicity, was observed in the caudate but not in the NAc.
Conclusions:
- Inhibition of GABAergic transmission in the nucleus accumbens is associated with METH behavioral sensitization.
- Activation of GABAergic transmission in the caudate is linked to METH-induced neurotoxicity.
- These findings highlight distinct regional roles of the GABAergic system in the neurobiological consequences of chronic METH exposure.
Related Concept Videos
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...
01:12GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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...
01:26Neurochemical Transmission: Sites of Drug Action
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
01:21Drugs Affecting Neurotransmitter Release or Uptake
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
01:25Adrenergic Agonists: Indirect-Acting Agents
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...