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Cholinergic Receptors: Nicotinic01:15

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Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
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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...
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Cholinergic Receptors: Muscarinic01:25

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The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
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Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

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Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
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Parasympathetic Signaling01:30

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Parasympathetic signaling plays a crucial role in regulating various physiological processes. It involves the release of acetylcholine (ACh) by parasympathetic neurons, which can have localized and short-lived effects. The majority of ACh released is rapidly inactivated at the synapse by the enzyme acetylcholinesterase (AChE), which hydrolyzes Ach into choline and acetate. Additionally, the tissue cholinesterase deactivates any ACh diffusing into the surrounding tissues.
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Cholinergic Neurons: Neurotransmission01:23

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Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
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Probing Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices via Laser Flash Photolysis of Photoactivatable Nicotine
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Impulsive behavior and nicotinic acetylcholine receptors.

Yu Ohmura1, Iku Tsutsui-Kimura, Mitsuhiro Yoshioka

  • 1Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. gwd0701@yahoo.co.jp

Journal of Pharmacological Sciences
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Impulsivity, a risk factor for addiction and suicide, is modulated by nicotinic acetylcholine receptors (nAChRs) in brain regions like the medial prefrontal cortex. Targeting these nAChR mechanisms may offer new treatments for impulsivity disorders.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Higher impulsivity is linked to addiction, criminal behavior, and suicide.
  • Excessive impulsivity is a hallmark of psychiatric disorders like ADHD and schizophrenia.
  • Nicotinic acetylcholine receptors (nAChRs) play a role in regulating impulsive behavior.

Purpose of the Study:

  • To review recent advances in understanding nAChR-related brain mechanisms modulating impulsivity.
  • To explore the role of dopamine release in the ventral striatum and mPFC.
  • To investigate the function of α4β2 nAChRs in the infralimbic cortex (mPFC).

Main Methods:

  • Review of existing scientific literature on nAChRs and impulsivity.
  • Analysis of studies focusing on dopamine pathways in reward and decision-making circuits.
  • Examination of research on specific nAChR subtypes, particularly α4β2, in prefrontal cortex regions.

Main Results:

  • nAChRs are integral to the neural circuitry underlying impulsive behavior.
  • Dopamine release in the ventral striatum and medial prefrontal cortex significantly influences impulsivity.
  • Specific nAChR subtypes, such as α4β2 in the infralimbic cortex, are key modulators of impulsive actions.

Conclusions:

  • Understanding nAChR-mediated neurotransmission offers potential therapeutic targets for impulsivity.
  • Targeting dopamine pathways and specific nAChRs in the mPFC could lead to novel treatments.
  • Further research into central nAChRs is crucial for developing effective interventions for impulsivity-related disorders.