NVS-GEN_ML2-NeurotransmittersFINAL

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Transcript NVS-GEN_ML2-NeurotransmittersFINAL

NEURO-PHARMACOLOGY OF NICOTINE
Mini-Lecture 2
Module: Tobacco and the Nervous System
Objectives of the Mini Lecture
Goals of Mini Lecture: Provide students with the
knowledge about nicotine action on the brain and how
nicotine causes craving and addiction.
Learning Objectives :
Students will be able to:
• Describe the pathways of nicotine action on the brain.
• Explain how nicotine causes craving and addiction.
Contents
Core Slides:
1. Nicotine
2. Pathways of Nicotine Action
3. How Nicotine Acts in the Brain (1-4)
Optional Slides:
1. Nicotine and Nicotinic Receptors
2. Alternate Pathway: GABA
CORE SLIDES
Neuro-Pharmacology of Nicotine
Mini Lecture 2
Module: Tobacco and The Nervous System
Nicotine
• Each cigarette contains
approx. 10 milligrams of
nicotine  a smoker gets
approx. 1 to 2 milligrams
from each cigarette.1
• Nicotine is shaped like
the neurotransmitter
acetylcholine.2
http://www.chm.bris.ac.uk/org/gallagher/nAChR.gif
1. Benowitz 1996; 2. National Institute on Drug Abuse. http://www.drugabuse.gov/JSP4/MOD2/page3.html
Pathways of Nicotine Action1
• Nicotine activates nicotinic
receptors in brain →
modulates immune response
by a or b pathways (figure):
• a → activation of the
hypothalamus–pituitary–
adrenal axis
• b → activation of the
autonomic nervous system
via sympathetic and parasympathetic innervations
a
b
http://www.nature.com/nri/journal/v2/n5/images/nri803-f3.gif
1. Figure reprinted from Sopori 2002
How Nicotine Acts in the Brain (1)
1) Nicotine (half-life: 40
minutes) mimics
actions of
acetylcholine.
2) Directly activates
dopamine systems in
brain → responsible
for mediating pleasure
response.
http://www.treatobacco.net/en/uploads/image/nach_receptors.jpg
1. School of Chemistry, Bristol University, UK. 2001. http://www.chm.bris.ac.uk/motm/nicotine/Emetabolisme.html
How Nicotine Acts in the Brain (2)
3) Blocks reabsorption of
dopamine and stimulates
release of more dopamine
through glutamate.
4) Prolonged nicotine
exposure → excessive and
chronic activation →
decreased dopamine
efficiency → reduced no. of
available receptors .
http://www.chm.bris.ac.uk/motm/nicotine/E-synapse.html
1. School of Chemistry, Bristol University, UK. 2001. http://www.chm.bris.ac.uk/motm/nicotine/Emetabolisme.html
How Nicotine Acts in the Brain (3)
5) Reduction in no. of active
receptors → decreased
psychotropic effect of
nicotine.
6) Leads to phenomenon of
tolerance → smoker
needs to smoke more
cigarettes just to create
normal levels of
dopamine.
http://www.chm.bris.ac.uk/motm/nicotine/E-concentr.html
1. School of Chemistry, Bristol University, UK. 2001. http://www.chm.bris.ac.uk/motm/nicotine/Emetabolisme.html
How Nicotine Acts in the Brain (4)
http://www.chm.bris.ac.uk/motm/nicotine/E-dependance.html
7) After brief abstinence (e.g., overnight) → reduced brain nicotine
→ receptors partially recover → increased dopamine receptor
sensitivity → increased neurotransmission rate abnormally →
induces craving.
1. School of Chemistry, Bristol University, UK. 2001. http://www.chm.bris.ac.uk/motm/nicotine/Emetabolisme.html
OPTIONAL SLIDES
Neuro-Pharmacology of Nicotine
Mini Lecture 2
Module: Tobacco and The Nervous System
Nicotine and Nicotinic Receptors1
http://www.chm.bris.ac.uk/motm/nicotine/E-metabolisme.html
Physiological normal conditions
After the opening of the canal by
binding to acethylcholine, the receptor
becomes desensitized before it goes
back to the state of rest or it is
regenerated.
Continuous exposure to tobacco
Nicotine substitutes for acetylcholine
and over-stimulates the nicotinic
receptor. The receptor is long-term
inactivated and its regeneration is
prevented by nicotine.
1. School of Chemistry, Bristol University, UK. 2001. http://www.chm.bris.ac.uk/motm/nicotine/Emetabolisme.html
Alternate Pathway: GABA1
• Nicotine also acts on
neurons producing
glutamate and GABA.
• Leads to a combination of
effects → amplifies
rewarding properties of
nicotine → promotes
addiction.
1. National Institute on Drug Abuse. 2003. http://www.drugabuse.gov/NIDA_Notes/NNVol17N6/Nicotine.html
The most important health message a doctor can give to
patients is to quit smoking.