Related Experiment Video
Updated: Jul 17, 2025
04:11
A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
17.0K
Prelimbic cortex dynorphin/κ opioid receptor system modulates methamphetamine-induced cognitive impairment
Ying-Jie Cheng1, Ying-Zhi Deng1, Di Deng1
1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Addiction Biology
|August 30, 2023
Summary
Chronic methamphetamine (METH) exposure impairs cognition. Blocking the dynorphin/kappa opioid receptor (KOR) system, particularly in the prelimbic cortex, may prevent these METH-induced cognitive deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Chronic methamphetamine (METH) use leads to persistent cognitive impairments.
- The endogenous dynorphin/kappa opioid receptor (KOR) system is implicated in stress and addiction.
- Understanding the specific neural circuits involved in METH-induced cognitive deficits is crucial.
Purpose of the Study:
- To investigate the role of the dynorphin/KOR system in methamphetamine-induced cognitive impairment.
- To identify the specific brain regions where the dynorphin/KOR system is activated by METH.
- To evaluate the therapeutic potential of KOR antagonists in mitigating METH-induced cognitive deficits.
Main Methods:
- Mice received daily METH injections (10 mg/kg) for seven days, followed by cognitive testing (novel object recognition, spontaneous alternation).
- KOR was systemically blocked using the antagonist norBNI or through genetic deletion (KOR knockout mice).
- Dynorphin and KOR mRNA levels were measured using quantitative PCR, with regional analysis in the prelimbic (PL) and infralimbic (IL) cortices. Localized PL injections of norBNI were also performed.
Main Results:
- METH administration induced significant cognitive impairment in mice.
- Systemic KOR blockade with norBNI or KOR deletion prevented METH-induced cognitive deficits.
- METH exposure increased dynorphin and KOR mRNA levels specifically in the prelimbic cortex (PL).
- Microinjection of norBNI into the PL reversed METH-induced cognitive impairments.
Conclusions:
- Activation of the dynorphin/KOR system within the prelimbic cortex is a key mechanism underlying METH-induced cognitive impairment.
- KOR antagonists demonstrate neuroprotective potential against cognitive deficits associated with chronic METH abuse.
- Targeting the dynorphin/KOR pathway offers a promising therapeutic strategy for treating drug abuse-related cognitive dysfunction.
Related Concept Videos
01:24CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
230
CNS stimulants, such as cocaine, amphetamines, and cannabinoids, have varying structures and mechanisms of action that lead to different therapeutic effects and side effects. Cocaine, with its molecular formula C17H21NO4, is a tropane alkaloid and a tertiary amino compound. It has two chemical forms: the hydrochloride salt and the "freebase." The former is in powder form, while the latter involves removing the hydrochloride salt to create a form that can be smoked. Cocaine exerts its...
230
01:15Drug Abuse and Addiction: Pharmacological Phenomena
508
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...
508
01:22Opioid Receptors: Overview
1.0K
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
1.0K
01:25Adrenergic Agonists: Indirect-Acting Agents
1.7K
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...
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...
1.7K
01:25Analgesia and Pain Management
654
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
654
01:29Drugs Affecting Neurotransmitter Synthesis
1.4K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.4K