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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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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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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

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Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists01:30

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Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
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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 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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Related Experiment Video

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Probing Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices via Laser Flash Photolysis of Photoactivatable Nicotine
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A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability.

Steven Storage1, Mark A Mandelkern, Jonathan Phuong

  • 1UCLA School of Medicine, Los Angeles, CA, USA; Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Psychiatry Research
|October 24, 2013
PubMed
Summary

People with higher harm avoidance, a personality trait linked to anxiety, have greater availability of nicotinic acetylcholine receptors (nAChRs). This suggests a biological link between cholinergic systems and anxiety-like behaviors.

Keywords:
Harm avoidanceNicotine dependenceNicotinic acetylcholine receptorPositron emission tomographyTemperament and Character InventoryTobacco

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A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
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Area of Science:

  • Neuroscience
  • Psychiatry
  • Psychology

Background:

  • Cholinergic neurotransmission plays a role in anxiety regulation.
  • Heightened cholinergic function may correlate with anxiety-like and harm-avoidant behaviors.

Purpose of the Study:

  • To investigate the association between harm avoidance (HA) temperament and alpha-4-beta-2 nicotinic acetylcholine receptor (α4β2* nAChR) availability.
  • To explore the biological underpinnings of personality dimensions related to anxiety.

Main Methods:

  • Positron emission tomography (PET) scanning with radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (2-FA).
  • Assessment of harm avoidance (HA) using the Temperament and Character Inventory (TCI) in 105 healthy adults (smokers and non-smokers).

Main Results:

  • A significant positive association was found between total HA scores and mean α4β2* nAChR availability.
  • Specific HA subscales, 'Fear of Uncertainty' and 'Fatigability,' also showed significant positive correlations with nAChR availability.

Conclusions:

  • Elevated harm avoidance is linked to greater α4β2* nAChR availability, suggesting a biological basis for anxiety-related personality traits.
  • Findings contribute to understanding the neurobiology of personality and may inform research into psychiatric disorders characterized by anxiety.