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NEURO-PHARMACOLOGY OF NICOTINE

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 :

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NEURO-PHARMACOLOGY OF NICOTINE

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  1. NEURO-PHARMACOLOGY OF NICOTINE Mini-Lecture 2 Module: Tobacco and the Nervous System

  2. 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.

  3. Contents Core Slides: • Nicotine • Pathways of Nicotine Action • How Nicotine Acts in the Brain (1-4) Optional Slides: • Nicotine and Nicotinic Receptors • Alternate Pathway: GABA

  4. CORE SLIDES Neuro-Pharmacology of Nicotine Mini Lecture 2 Module: Tobacco and The Nervous System

  5. 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

  6. 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 para-sympathetic innervations a b http://www.nature.com/nri/journal/v2/n5/images/nri803-f3.gif 1. Figure reprinted from Sopori 2002

  7. 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/E-metabolisme.html

  8. 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/E-metabolisme.html

  9. 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/E-metabolisme.html

  10. How Nicotine Acts in the Brain (4) 7) After brief abstinence (e.g., overnight) → reduced brain nicotine → receptors partially recover → increased dopamine receptor sensitivity → increased neurotransmission rate abnormally → induces craving. http://www.chm.bris.ac.uk/motm/nicotine/E-dependance.html 1. School of Chemistry, Bristol University, UK. 2001. http://www.chm.bris.ac.uk/motm/nicotine/E-metabolisme.html

  11. OPTIONAL SLIDES Neuro-Pharmacology of Nicotine Mini Lecture 2 Module: Tobacco and The Nervous System

  12. 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/E-metabolisme.html

  13. 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

  14. The most important health message a doctor can give to patients is to quit smoking.

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