1. Copyright © 2008 Pearson Allyn & Bacon Inc. 1 Chapter 4 Psychopharmacology This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network preparation of any derivative work, including the extraction, in whole or in part, of any images any rental, lease or lending of the program.

2. Copyright © 2008 Pearson Allyn & Bacon Inc. 2 Chapter 4 Outline Principles of Psychopharmacology Sites of Drug Action Neurotransmitters and Neuromodulators

3. Copyright © 2008 Pearson Allyn & Bacon Inc. 3 Principles of Psychopharmacology Psychopharmacology The study of _____________________________________________. Drug effects The changes a drug produces in an animal’s physiological processes and behavior. Sites of _______________ The locations at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells.

4. Copyright © 2008 Pearson Allyn & Bacon Inc. Drug effects example: Effects of opiates (_______________________) decrease sensitivity to pain, slow down digestion, relax muscles, constrict pupils, induce euphoria Sites of action – specialized receptors in certain neurons in the CNS. 4

5. Copyright © 2008 Pearson Allyn & Bacon Inc. 5 Principles of Psychopharmacology Pharm_______________ (movement of drugs) The process by which drugs are absorbed, distributed within the body, metabolized, and excreted. Once a drug enters the body it begins to be ______________________________________________ _____________________________________________.

6. Copyright © 2008 Pearson Allyn & Bacon Inc. 6 Principles of Pharmacology Routes of administration Intravenous (IV) injection Injection of a substance directly into a _____. Usually the fastest route Intraperitoneal (IP) injection The injection of a substance into the ______________________________________________ ___________surrounds the stomach, intestines, liver, and other abdominal organs. Used with small animals.

7. Copyright © 2008 Pearson Allyn & Bacon Inc. 7 Principles of Pharmacology Routes of administration Intramuscular (IM) injection Injection of a substance into a muscle. Absorbed by _________________that supply the muscle. ______________________ (SC) injection Injection of a substance into the space beneath the skin. (TB test). Oral administration Administration of a substance into the mouth, so it is swallowed. (Some drugs are destroyed by digestive ________________).

8. Copyright © 2008 Pearson Allyn & Bacon Inc. 8 Principles of Pharmacology Routes of administration ________________administration Administration of a substance by placing it beneath the tongue. (Nitroglycerine for coronary artery dilation). Intrarectal administration Administration of a substance into the rectum. (suppository). Inhalation Administration of a vaporous substance into the lungs. (_________________ effects).

9. Copyright © 2008 Pearson Allyn & Bacon Inc. 9 Principles of Pharmacology Routes of administration Topical administration Administration of a substance absorbed through the __________. (Nicotine patch). Intracerebral administration (Some drugs cannot cross the _______________________). Administration of a substance directly into the brain. Intracerebroventricular (ICV) administration Administration of a substance into one of the cerebral ventricles.

10. Copyright © 2008 Pearson Allyn & Bacon Inc. 10 Principles of Pharmacology Drug Effectiveness: lipid soluble drugs _____ the blood/brain barrier, water soluble drugs ________. Dose-response curve Plots the magnitude of the effect of a drug as a function of the amount of the drug administered. Therapeutic index The ratio between the dose that produces the desired effect in 50% of the animals and the dose that produces ________ effects in 50% of the animals.

11. Copyright © 2008 Pearson Allyn & Bacon Inc. Most drugs have more than one effect. Opiates reduce pain (1), and also depress heart rate and respiration which can be lethal (2). The therapeutic index differs for different classes of drugs. Barbiturates 2-3. Tranquilizers (100+). 11

12. Copyright © 2008 Pearson Allyn & Bacon Inc. 12 Principles of Pharmacology Drug Effectiveness ______________: The readiness with which two molecules join together. High affinity drugs produce effects at low concentrations. Low affinity drugs require high concentrations to have an effect.

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16. Copyright © 2008 Pearson Allyn & Bacon Inc. 16 Principles of Pharmacology Effects of repeated administration ________________ (most common pattern) A decrease in the effectiveness of a drug that is administered repeatedly. __________________ (less common, bee stings) An increase in the effectiveness of a drug that is administered repeatedly.

17. Copyright © 2008 Pearson Allyn & Bacon Inc. 17 Principles of Pharmacology Effects of repeated administration ________________ symptom The appearance of symptoms opposite to those produced by a drug when the drug is administered repeatedly and then suddenly no longer taken. ____________ An inert substance given to an organism in lieu of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug.

18. Copyright © 2008 Pearson Allyn & Bacon Inc. Because drugs may have multiple sites of action, the drug effect at some sites may show tolerance, but at other sites tolerance may not be expressed! Tolerance is the result of the body’s attempt to ______________ for the effects of the drug. (Preserve homeostasis). Barbituates cause sedation, and depress respiration. The sedation effect shows tolerance, the depression of respiration does not! 18

19. Copyright © 2008 Pearson Allyn & Bacon Inc. 19 Sites of Drug Action ________________ A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell. _______________ A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell.

20. Copyright © 2008 Pearson Allyn & Bacon Inc. 20 Sites of Drug Action Effects on receptors Direct agonist A drug that binds with and activates a receptor. This drug mimics the effects of a neurotransmitter. ________________blocker A drug that binds with a receptor but does not activate it; prevents the natural ligand from binding with the receptor.

21. Copyright © 2008 Pearson Allyn & Bacon Inc. 21 Sites of Drug Action Effects on receptors Direct antagonist Synonym for a receptor blocker. Noncompetitive binding Binding of a drug to a site on a receptor; does not interfere with the binding site for the principal ligand.

22. Copyright © 2008 Pearson Allyn & Bacon Inc. 22 Sites of Drug Action Effects on receptors Indirect antagonist A drug that attaches to a binding site on a receptor and interferes with the action of the receptor; does not interfere with the binding of the ___________________. Indirect agonist A drug that attaches to a binding site on a receptor and facilitates the action of the receptor; does not interfere with the binding site of the principal ligand.

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25. Copyright © 2008 Pearson Allyn & Bacon Inc. Summary: Drugs can _________________________________________ _________________________________________ _________________________________________ _________________________________________ _________________________________________ _________________________________________ _________________________________________ ________________________________________. 25

26. Copyright © 2008 Pearson Allyn & Bacon Inc. Overview: In the brain most synaptic communication is accomplished by just two neurotransmitters. Glutamate – _______________ GABA – ___________________ Glycerine – inhibitory in spinal cord & lower brain stem. In general the other neurotransmitters serve as _________________and act to activate or inhibit entire circuits. Ach activates learning circuits, but what is learned is transmitted by glutamate and GABA neurons. Norepinephrine – heightens vigilance. Serotonin – suppresses some species-typical behaviors. 26

27. Copyright © 2008 Pearson Allyn & Bacon Inc. 27 Neurotransmitters and Neuromodulators Acetylcholine The primary neurotransmitter secreted by the efferent axons of the central nervous system. All muscular movement is accomplished by the release of acetylcholine. Appears to be involved in regulating REM sleep, perceptual learning, and memory.

28. Copyright © 2008 Pearson Allyn & Bacon Inc. 28 Neurotransmitters and Neuromodulators Acetylcholine Acetyl-CoA A cofactor that supplies acetate for the synthesis of acetylecholine. Choline acetyltransferase (ChAT) The enzyme that transfers the acetate ion from acetyl coenzyme A to choline, producing the neurotransmitter acetylcholine.

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31. Copyright © 2008 Pearson Allyn & Bacon Inc. 31 Neurotransmitters and Neuromodulators Acetylcholine Botulinum toxin An acetylcholine antagonist; prevents release by terminal buttons. Black widow spider venom A poison produced by the black widow spider that triggers the release of acetylcholine. Neostigmine A drug that inhibits the activity of acetylcholinesterase.

32. Copyright © 2008 Pearson Allyn & Bacon Inc. 32 Neurotransmitters and Neuromodulators Acetylcholine (two receptors) _______________receptor An ionotropic acetylcholine receptor that is stimulated by nicotine and blocked by curare. (Rapid action, used at neuromuscular junction). ____________________receptor A metabotropic acetylcholine receptor that is stimulated by muscarine and blocked by atropine. (Second messenger results in slower and more prolonger action. This is the main receptor in CNS.)

33. Copyright © 2008 Pearson Allyn & Bacon Inc. 33 Neurotransmitters and Neuromodulators Acetylcholine ______________ A drug that blocks muscarinic acetylcholine receptors. A belladonna alkaloid extracted from nightshade. This drug was used to increase _______________. Curare A drug that blocks nicotinic acetylcholine receptors and causes paralysis. In surgery a anesthetic must also be used, because the person is _________________________________, even though they are paralyzed.

34. Copyright © 2008 Pearson Allyn & Bacon Inc. 34 Neurotransmitters and Neuromodulators Monoamines ______________ Dopamine (DA) Norepinephrine (NE) Epinephrine Indolamines Serotonin (5-HT)

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36. Copyright © 2008 Pearson Allyn & Bacon Inc. 36 Neurotransmitters and Neuromodulators _________________ A class of amines that includes indolamines such as serotonin and catecholamines such as dopamine, norepinephrine, and epinephrine.

37. Copyright © 2008 Pearson Allyn & Bacon Inc. 37 Neurotransmitters and Neuromodulators Monoamines __________________ A neurotransmitter; one of the catecholamines. Produces both excitatory and inhibitory postsynaptic potentials. Implicated roles in movement, attention, learning, reinforcing effects of abused drugs. Synthesized from tyrosine that we obtain from our diet.

38. Copyright © 2008 Pearson Allyn & Bacon Inc. 38 Neurotransmitters and Neuromodulators Monoamines-dopamine L-Dopa The biologically active form of DOPA; the precursor of the catecholamines; often used to treat Parkinson’s disease because of its role as a dopamine agonist. Side-effect is heightened_______________.

39. Copyright © 2008 Pearson Allyn & Bacon Inc. 39 Neurotransmitters and Neuromodulators Monoamines-dopamine ___________________ system A system of neurons originating in the substantia nigra and terminating in the neostriatum (caudate nucleus and putamen of the basal ganglia); appears to play a role in the control of ______________.

40. Copyright © 2008 Pearson Allyn & Bacon Inc. 40 Neurotransmitters and Neuromodulators Monoamines-dopamine __________________system A system of dopaminergic neurons originating in the ventral tegmental area and terminating in the nucleus accumbens, amygdala, and hippocampus; appears to play a role in the ___________________of drugs that are commonly abused.

41. Copyright © 2008 Pearson Allyn & Bacon Inc. 41 Neurotransmitters and Neuromodulators Monoamines-dopamine _______________ system A system of dopaminergic neurons originating in the ventral tegmental area and terminating in the prefrontal cortex; appears to influence formation of short-term memories, ___________________________________________.

42. Copyright © 2008 Pearson Allyn & Bacon Inc. 42 Neurotransmitters and Neuromodulators Monoamines-dopamine ________________ disease A neurological disease characterized by tremors, rigidity of the limbs, poor balance, and difficulty initiating movements; caused by degeneration of the nigrostriatal system; Parkinson’s disease has been treated with L-DOPA.

43. Copyright © 2008 Pearson Allyn & Bacon Inc. 43 Neurotransmitters and Neuromodulators Monoamines-dopamine AMPT A drug that blocks the activity of tyrosine hydroxylase and thus interferes with the synthesis of the catecholamines. _________________ A drug that interferes with the storage of monoamines in synaptic vesicles; serves as a monoamine antagonist.

44. Copyright © 2008 Pearson Allyn & Bacon Inc. 44 Neurotransmitters and Neuromodulators Monoamines-dopamine Methylphenidate A drug that inhibits the reuptake of dopamine; also known as ____________; used to treat children with attention deficit disorder.

45. Copyright © 2008 Pearson Allyn & Bacon Inc. 45 Neurotransmitters and Neuromodulators Monoamines-dopamine _________________________ (MAO) A class of enzymes that destroy the monoamines; dopamine, norepinephrine, and serotonin. deprenyl A drug that blocks the activity of MAO-B; acts as a dopamine agonist.

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47. Copyright © 2008 Pearson Allyn & Bacon Inc. 47 Neurotransmitters and Neuromodulators Monoamines-dopamine _____________________ A drug that reduces the symptoms of schizophrenia by blocking dopamine D 2 receptors.

48. Copyright © 2008 Pearson Allyn & Bacon Inc. 48 Neurotransmitters and Neuromodulators Monoamines-norepinephrine (NE) _________________________ One of the catecholamines; a neurotransmitter found in the brain and in the sympathetic division of the autonomic nervous system. Epinephrine One of the catecholamines; a hormone secreted by the adrenal medulla; serves as a neurotransmitter in the brain. The same molecule can be used as both a hormone and neurotransmitter.

49. Copyright © 2008 Pearson Allyn & Bacon Inc. 49 Neurotransmitters and Neuromodulators Monoamines-norepinephrine (NE) Norepinephrine is synonymous with nor______________. Found in neurons of the brain and the autonomic nervous system. Almost every region of the brain receives input from noradrenergic neurons. Implicated to play central role in _______________________________________________.

50. Copyright © 2008 Pearson Allyn & Bacon Inc. 50 Neurotransmitters and Neuromodulators Monoamines-norepinephrine (NE) Fusaric acid A drug that inhibits the activity of the enzyme dopamine-ß-hydroxylase and thus blocks the production of norepinephrine. ____________ would be secreted as a result. Locus coeruleus A dark-colored group of noradreneric cell bodies located in the pons near the rostral end of the floor of the fourth ventricle.

51. Copyright © 2008 Pearson Allyn & Bacon Inc. 51 Neurotransmitters and Neuromodulators Monoamines-norepinephrine (NE) Axonal varicosity An enlarged region along the length of an axon that contains synaptic vesicles and releases a neurotransmitter or neuromodulator. Idazoxan A drug that blocks presynaptic noradrenergic  2 receptors and hence acts as an agonist, stimulating the synthesis and release of NE.

52. Copyright © 2008 Pearson Allyn & Bacon Inc. 52 Neurotransmitters and Neuromodulators Monoamines _______________ Serotonin is an indolamine neurotransmitter. Also called 5-HT or 5-hydroxytryptamine. Thought to play a role in the regulation of _________, the control of eating, sleep, dreaming, and arousal. Also thought to be involved in the regulation of pain. The amino acid tryptophan is the precursor of serotonin.

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54. Copyright © 2008 Pearson Allyn & Bacon Inc. 54 Neurotransmitters and Neuromodulators Monoamines-serotonin (5-HT)  PCPA A drug that inhibits the activity of tryptophan hydroxylase and thus interferes with the synthesis of 5-HT and serves as a serotonergic antagonist.  Fluoxetine (Prozac) A drug that inhibits the reuptake of 5-HT. Used to treat depression, obsessive-compulsive disorder and some anxiety disorders. There are at least ________________ serotonin receptors. Different drugs may selectively effect different receptors.

55. Copyright © 2008 Pearson Allyn & Bacon Inc. 55 Neurotransmitters and Neuromodulators Monoamines-serotonin (5-HT)  Fenfluramine A drug that stimulates the release of 5-HT.  __________ A drug that stimulates 5-HT 2A receptors.

56. Copyright © 2008 Pearson Allyn & Bacon Inc. 56 Neurotransmitters and Neuromodulators Monoamines-  MDMA A drug that serves as a noradrenergic and serotonergic agonist, also known as _____________ has excitatory and hallucinogenic effects. MDMA damages serotonin pathways.

57. Copyright © 2008 Pearson Allyn & Bacon Inc. 57 Neurotransmitters and Neuromodulators Amino acids The most common amino acid transmitters are: Glutamate Gamma-aminobutyric acid (GABA) Glycine

58. Copyright © 2008 Pearson Allyn & Bacon Inc. 58 Neurotransmitters and Neuromodulators Monoamines-glutamate  _______________ An amino acid; the most important excitatory neurotransmitter in the brain.  NMDA receptor A specialized ionotropic glutamate receptor that controls a calcium channel that is normally blocked by Mg 2+ ions; has several other binding sites.  AMPA receptor An ionotrpoic glutame receptor that controls a sodium channel; stimulated by AMPA.

59. Copyright © 2008 Pearson Allyn & Bacon Inc. Glutamate receptors: Three types of iontropic glutamate receptors. Seven subtypes of metabotropic glutamate receptors. 59

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61. Copyright © 2008 Pearson Allyn & Bacon Inc. 61 Neurotransmitters and Neuromodulators Amino acids—glutamate Kainate receptor An ionotropic glutamate receptor that controls a sodium channel; stimulated by kainic acid. Metabotropic glutamate receptor A category of metabotropic receptors sensitive to glutamate.

62. Copyright © 2008 Pearson Allyn & Bacon Inc. 62 Neurotransmitters and Neuromodulators Amino acids—glutamate AP5 A drug that blocks the glutamate binding site on NMDA receptors and impairs certain forms of learning. PCP (Phencyclidine) A drug that binds with the PCP binding site of the NMDA receptor and serves as an indirect antagonist of glutamate.

63. Copyright © 2008 Pearson Allyn & Bacon Inc. 63 Neurotransmitters and Neuromodulators Amino acids GABA Gamma-aminobutyric acid is an amino acid. GABA is the most important ______________ neurotransmitter in the brain and spinal cord. Allyglycine A drug that inhibits the activity of GAD and thus blocks the synthesis of GABA.

64. Copyright © 2008 Pearson Allyn & Bacon Inc. 64 Neurotransmitters and Neuromodulators Amino acids—GABA ______________ A direct agonist for the GABA binding site on the GABA A receptor. Bicuculline A direct antagonist for the GABA binding site on the GABA A receptor.

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66. Copyright © 2008 Pearson Allyn & Bacon Inc. 66 Neurotransmitters and Neuromodulators Amino acids—GABA ___________________ A category of anxiolytic drugs; an indirect agonist for the GABA A receptor; these drugs are used for their tranquilizing effects. Examples of these drugs include Valium (diazepam) and Librium (chlordiazepoxide). ___________________ An anxiety-reducing effect.

67. Copyright © 2008 Pearson Allyn & Bacon Inc. The brain does not produce valium, barbituates, or picrotoxin. What are the natural ligands for these binding sites? Research has not answered this question. It is assumed that these binding sites are not an accident, and that brain chemicals use them, but they have not yet been identified. 67

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69. Copyright © 2008 Pearson Allyn & Bacon Inc. 69 Neurotransmitters and Neuromodulators Amino acids ______________ It appears to be the most important inhibitory neurotransmitter in the lower brain stem and spinal cord. Strychnine A direct antagonist for the glycine receptor. Causes convulsions and death even in small doses.

70. Copyright © 2008 Pearson Allyn & Bacon Inc. 70 Neurotransmitters and Neuromodulators Peptides (Two or more amino acids linked together by peptide bonds) Neurons of the central nervous system release a large variety of peptides. A neuron manufactures both the polypeptides and the enzymes that it needs to break them apart.

71. Copyright © 2008 Pearson Allyn & Bacon Inc. 71 Neurotransmitters and Neuromodulators Peptides Synthesis takes place in the soma. They are delivered to the terminal buttons by axoplasmic transport. Most peptides appear to serve as ______________, while some act as neurotransmitters.

72. Copyright © 2008 Pearson Allyn & Bacon Inc. 72 Neurotransmitters and Neuromodulators Peptides __________________opioid A class of peptides secreted by the brain that act as opiates; drugs that effect opioid receptors reduce ______. Enkephalin One of the endogenous opioids. At least three different opioid receptors. Naloxone A drug that blocks opioid receptors; often used to treat heroin overdose.

73. Copyright © 2008 Pearson Allyn & Bacon Inc. 73 Neurotransmitters and Neuromodulators Lipids Endocannabinoid A lipid; an endogenous ligand for receptors that bind with ______, the active ingredient of marijuana. Anandamide The first cannabinoid to be discovered and probably the most important one.

74. Copyright © 2008 Pearson Allyn & Bacon Inc. 74 Neurotransmitters and Neuromodulators Lipids Rimonabant A drug that blocks cannabinoid CB 1 receptors. THC produces analgesia, sedation, reduces nausea, stimulates appetite, but impairs concentration and memory. May distort time perception and change sensory perception. THC can be ______________________________________________ ______________, the THC is _________________into the CNS.

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76. Copyright © 2008 Pearson Allyn & Bacon Inc. 76 Neurotransmitters and Neuromodulators Nucleosides Adenosine A combination of ribose and adenine. Released by glial cells and neurons. Dilates blood vessels and increases supply of cellular nutrients. ________________ A bitter-tasting alkaloid drug that blocks adenosine receptors. Adenosine tends to suppress neural activity, and caffeine counters this suppression.

77. Copyright © 2008 Pearson Allyn & Bacon Inc. 77 Neurotransmitters and Neuromodulators Soluble gases _________________ (NO) A gas produced by cells in the nervous system; used as a means of communication between cells. Influences blood vessel dilation, and may play a role in sexual arousal. Nitric oxide synthase The enzyme responsible for production of nitric oxide.