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NEUROTRANSMITTERS & NEUROPHARMACOLOGY

 

TABLE OF CONTENTS

Updated: Feb. 5, 2008

LECTURE INFORMATION

KEY CONCEPTS IN THIS LECTURE

1. Communication between neurons involves secretion of neurotransmitter at the nerve terminal. Neurotransmitters are small molecular weight molecules which diffuse easily across the synapse and have a short-term effect. There are several common neurotransmitters (Acetylcholine, Norepinephrine, Serotonin, Dopamine, Glutamate and GABA), each of which acts at 2 or more receptor types. For example, Acetylcholine has two receptor types, nicotinic and muscarinic.

2. Pharmacology is the study drug effects on living systems. Most drugs alter CNS function by acting at the level of the neurotransmitter. Drugs can alter neurotransmitter synthesis, packaging, release, reuptake, catabolism, or receptor function. Drugs are used to dissect the specifics of a neural pathway and to treat neural dysfunction.

3. Neuropeptides are larger molecular weight molecules which are secreted by nerves and which have longer-lasting effects than a neurotransmitter. They often act in concert with a neurotransmitter. Substance P and Neuropeptide Y are examples of neuropeptides.

LECTURE OUTLINE

I. PHARMACOLOGY AND NERVE FUNCTION	

  A. Introduction
     1. Pharmacology is the study of drug effect on living systems.
          a. How are drugs used to understand neural function
              and behavior.

  B. Drugs and the nervous system **
     1. Brief review of neurotransmitter physiology
          a. Neurotransmitters can be excititory, inhibitory, or both
          b. Principles of neurotransmitter-receptor binding
          c. Law of Mass Action applies to receptor function
               1) KD
                    a) What it means and how it is used
          d. Up- and Down-regulation of receptors
               1) Implications for addiction and medical drug use
               2) Role of VTA, dopamine, and nuc. accumbens
               3) Single neurons in nuc. accumbens respond to drugs alone
               4) What is the normal function for this pathway? 
     2. General drug actions on the Nervous System 
          a. Drugs often target neurotransmitter function
               1) There are a number of mechanisms (release, reuptake, etc.)
          b. Gilal cells recycle some neurotransmitters **

  C. Drug action at the postsynaptic receptor
     1. Competitive and non-competitive effects **
          a. Receptor physiology can be complex (GABAA receptor)
          b. KD and competitive inhibition 
     2. An exercise: Determining a new drug's action

II. INTRODUCTION TO NEUROTRANSMITTERS 	

  A. General characteristics of the "classical" neurotransmitters
     1. Small molecular weight
     2. Fast-acting
     3. Multiple neurotransmitters often affect post-synaptic responses in nerves
     4. Neurotransmitters have more than one receptor subtype
     5. The response to a neurotransmitter is tissue-specific
          a. Recall Ach's different actions on heart and skeletal muscle 

III. BRAIN DISTRIBUTION OF NEUROTRANSMITTERS

  A. Some Terminology
     1. Monoamines, amino acids, and peptide neurotransmitters

  B. Brain Pathways	
     1. Acetylcholine (Ach) **
     2. Dopamine (DA)
     3. Norepinephrine (=Noradrenalin, NE)
     4. Serotonin (=5-Hydroxytryptamine, 5-HT)
     5. Glutamatic acid (=Glutamate, Glu)
     6. Gamma-aminobutyric acid (GABA)
     7. Glycine (Gly)
     8. Enkephalin (endogenous opioid) **

IV. NEUROPEPTIDES	

  A. General characteristics of neuropeptides and neuromodulators
     1. Larger molecular weight
     2. Slower-acting (minutes, hours)
     3. Can act in concert with a neurotransmitter
     4. Like neurotransmitters, there is more than one 
         receptor subtype, and the response is tissue-specific

  B. Example: Substance P
     1. Sunburn and release of Substance P and Glutamate
          a. Substance P is a neuromodulator, a substance that changes
              neurotransmitter effectivenss

  C. Example: Neuropeptide Y and feeding behavior

STUDY QUESTIONS

  1. Read about the routes of drug adminstration in the text. What are the advantages and disadvantages of the various routes of administration?
  2. Compare and contrast neurotransmitter and neuropeptide action.
  3. What is the advantage of having multiple receptor subtypes for a neurotransmitter or neuropeptide? How are drugs used to identify a receptor subtype? Explain.
  4. What is the Law of Mass Action and how does it apply to ligand receptor function? How is it used in the drug industry to test the efficacy of new drugs? What is up- and down-regulation of receptors? What is the physiological significance of up- and down-regulation? Give some examples.
  5. List the ways in which a drug might affect neurotransmitter function. For each way, give an example of a specific drug and how it works (see Carlson Figure 4.5 and Table 4.4). You do not have to memorize all the drugs and their actions. If you need to know what they do, you can look them up.
  6. What is autoregulation and how is it important in neurotransmitter function? Give an example.
  7. What are autoreceptors and how do they work? Heteroreceptors?
  8. What are monoamine oxidase (MAO) inhibitors and how do they alter neurotransmitter function?
  9. List some of the receptor subtypes for the common neurotransmitters (See Figure).
  10. Define and give the physiological significance (how or why it is important) for the following terms:
    • Pharmacokinetics
    • Dose response curve
    • Margin of safety (for a drug)
    • Placebo
    • Drug sensitization
    • Agonist
    • Antagonist

  11. What are the differences between competitive inhibition and non-competitive inhibition?
  12. Define drug tolerance and withdrawal symptoms. How are they related (see Text)?
  13. Relate receptor structure to its function (e.g. NMDA receptor for glutamate or GABAa receptor) (See Figs. 4.19 and 4.20)
  14. What approach might you employ to establish that a specific receptor subtype is present in a particular target cell? Explain.
  15. How are glial cells involved in the processing of neurotransmitter?
  16. Schizophrenia is thought to be caused by excess dopamine in certain brain regions. Drug therapy to alleviate schizophrenia by blocking dopamine can result in side effects resembling Parkinson-like symptoms (e.g., tremor of the hand). Explain why this might happen.
  17. List the "classic" neurotransmitters. Review in Carlson where in the brain the neurons originate for each neurotransmitter (Read the section entitled "Neurotransmitters and Neuromodulators" in the text. Don't memorize all of the information on drugs, however.) What are the general functions for each neurotransmitter in the central nervous system? Are they excititory, inhibitory, or both? Which neurotransmitters are considered monoamines? Catecholamines? Indoleamines? Amino acids? Peptides?
  18. What are adenosine and nitric oxide? How do they act as neurotransmitters? (See text)

ADDITIONAL INFORMATION ON THE INTERNET

Neurotransmitters. Neurotransmitter and neuromodulator function with some animations.

Animations on how a number of addictive drugs affect neural transmission.
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