1. Copyright © 2004 Allyn and Bacon 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 © 2004 Allyn and Bacon 2  Psychopharmacology  Psychopharmacology: The study of the effects of drugs on the nervous system and on behavior.  Drug effects: The changes a drug produces in an animal’s physiological processes and behavior.  Sites of Action: 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.

3. Copyright © 2004 Allyn and Bacon 3  Principles of Psychopharmacology  Pharmacokinetics  Pharmacokinetics: The process by which drugs are absorbed, distributed within the body, metabolized, and excreted.

4. Copyright © 2004 Allyn and Bacon 4  Principles of Pharmacology  Routes of Administration  Intravenous (IV) injection: Injection of a substance directly into a vein.  Intraperitoneal (IP) injection: The Injection of a substance into the peritoneal cavity-the space that surrounds the stomach, intestines, liver, and other abdominal organs.

5. Copyright © 2004 Allyn and Bacon 5  Principles of Pharmacology  Routes of Administration  Intramuscular (IM) injection: Injection of a substance into a muscle.  Subcutaneous (SC) injection: Injection of a substance into the space beneath the skin.  Oral administration: Administration of a substance into the mouth, so it is swallowed.

6. Copyright © 2004 Allyn and Bacon 6  Principles of Pharmacology  Routes of Administration  Sublingual administration: Administration of a substance by placing it beneath the tongue.  Intrarectal administration: Administration of a substance into the rectum.  Inhalation: Administration of a vaporous substance into the lungs.

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8. 8  Principles of Pharmacology  Routes of Administration  Topical administration: Administration of a substance by placing it beneath the tongue.  Intracerebral administration: Administration of a substance directly into the brain.  Intracerebroventricular (ICV) administration: Administration of a substance into one of the cerebral ventricles.

9. Copyright © 2004 Allyn and Bacon 9  Principles of Pharmacology  Distribution of Drugs Within the Body  Depot Binding: Binding of a drug with various tissues of the body or with proteins in the blood.  Albumin: A protein found in the blood, serves to transport free fatty acids and can bind with some lipid soluble drugs.

10. Copyright © 2004 Allyn and Bacon 10  Principles of Pharmacology  Drug Effectiveness  Dose-response curve: A graph of the magnitude of an 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 toxic effects in 50% of the animals.  Affinity: The readiness with which two molecules join together.

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13. 13  Principles of Pharmacology  Effects of Repeated Administration  Tolerance: A “decrease” in the effectiveness of a drug that is administered repeatedly.  Sensitization: An “increase” in the effectiveness of a drug that is administered repeatedly.

14. Copyright © 2004 Allyn and Bacon 14  Principles of Pharmacology  Effects of Repeated Administration  Withdrawal symptom: The appearance of symptoms opposite to those produced by a drug when the drug is administered repeatedly and then suddenly no longer taken.

15. Copyright © 2004 Allyn and Bacon 15  Principles of Pharmacology  Placebo Effects  Placebo: 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.

16. Copyright © 2004 Allyn and Bacon 16  Sites of Drug Action  Antagonist: A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell.  Agonist: A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell.

17. Copyright © 2004 Allyn and Bacon 17  Sites of Drug Action  Effects on Receptors  Direct agonist: A drug that binds with and activates a receptor.  Receptor blocker: A drug that binds with a receptor but does not activate it; prevents the natural ligand from binding with the receptor.

18. Copyright © 2004 Allyn and Bacon 18  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.

19. Copyright © 2004 Allyn and Bacon 19  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 principal ligand.  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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22. 22  Sites of Drug Action  Effects on Receptors  Presynaptic heteroreceptor: A receptor located in the membrane of a terminal button that receives input from another terminal button by means of an axoaxonic synapse; binds with the neurotransmitter released by the presynaptic terminal button.

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24. 24  Neurotransmitters and Neuromodulators  Acetylcholine  The first transmitter to be discovered.  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.

25. Copyright © 2004 Allyn and Bacon 25  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.

26. Copyright © 2004 Allyn and Bacon 26  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.  Hemicholinium: A drug that inhibits the uptake of choline.

27. Copyright © 2004 Allyn and Bacon 27  Neurotransmitters and Neuromodulators  Acetylcholine  Nicotinic receptor: An ionotropic acetylcholine receptor that is stimulated by nicotine and blocked by curare.  Muscarinic receptor: A metabotropic acetylcholine receptor that is stimulated by muscarine and blocked by atropine.  Atropine: A drug that blocks muscarinic acetylcholine receptors.  Curare: A drug that blocks nicotinic acetylcholine receptors.

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31. 31  Neurotransmitters and Neuromodulators  Monoamines  Catecholamines Dopamine (DA) Norepinephrine (NE) Epinephrine  Indolamines Serotonin (5-HT)

32. Copyright © 2004 Allyn and Bacon 32  Neurotransmitters and Neuromodulators  Monoamines  Monoamine: A class of amines that includes indolamines such as serotonin and catecholamines such as dopamine, norepinephrine, and epinephrine.  Indolamines Serotonin (5-HT)

33. Copyright © 2004 Allyn and Bacon 33  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Dopamine: A neurotransmitter; one of the catecholamine. 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.

34. Copyright © 2004 Allyn and Bacon 34  Neurotransmitters and Neuromodulators  Monoamines Dopamine  L-Dopa: The levorotatory form of DOPA; the precursor of the catecholamines; often used to treat Parkinson’s disease because of its as a dopamine agonist.

35. Copyright © 2004 Allyn and Bacon 35  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Nigrostriatal 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 movement.

36. Copyright © 2004 Allyn and Bacon 36  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Mesolimbic 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 reinforcing effects of drugs that are commonly abused.

37. Copyright © 2004 Allyn and Bacon 37  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Mesocortical 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, planning, and preparing strategies for problem solving.

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40. 40  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Parkinson’s Disease: A neurological disease characterized by tremors, rigidity of the limbs, poor balance, and difficulty in initiating movements; caused by degeneration of the nigrostriatal system; Parkinson’s disease has been treated with L-DOPA.

41. Copyright © 2004 Allyn and Bacon 41  Neurotransmitters and Neuromodulators  Monoamines Dopamine  AMPT: A drug that blocks the activity of tyrosine hydroxylase and thus interferes with the synthesis of the catecholamines.  Reserpine: A drug that interferes with the storage of monoamines in synaptic vesicles; serves as a monoamine antagonist.

42. Copyright © 2004 Allyn and Bacon 42  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Apomorphine: A drug that blocks dopamine autoreceptors at low doses; at high doses blocks postsynaptic receptors as well.  Methylphenidate: A drug that inhibits the reuptake of dopamine; also known as “Ritalin”; used to treat children with attention deficit disorder.

43. Copyright © 2004 Allyn and Bacon 43  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Monoamine oxidase (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.

44. Copyright © 2004 Allyn and Bacon 44  Neurotransmitters and Neuromodulators  Monoamines Dopamine  Chlorpromazine: A drug that reduces the symptoms of schizophrenia by blocking dopamine D 2 receptors.  Clozapine: A drug that reduces the symptoms of schizophrenia, apparently by blocking dopamine D 4 receptors.

45. Copyright © 2004 Allyn and Bacon 45  Neurotransmitters and Neuromodulators  Monoamines Norepinephrine (NE)  Norepinephrine is synonymous with noradrenaline.  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 vigilance or attentiveness to events in the environment.

46. Copyright © 2004 Allyn and Bacon 46  Neurotransmitters and Neuromodulators  Monoamines Norepinephrine (NE)  Norepinephrine: One of the catecholamines; a neurotransmitter found in the brain and in the sympathetic division of the autonomic nervous system.  Epinephrine: One of the catecholamies; a hormone secreted by the adrenal medulla; serves as a neurotransmitter in the brain.

47. Copyright © 2004 Allyn and Bacon 47  Neurotransmitters and Neuromodulators  Monoamines Norepinephrine (NE)  Norepinephrine: One of the catecholamines; a neurotransmitter found in the brain and in the sympathetic division of the autonomic nervous system.  Epinephrine: One of the catecholamies; a hormone secreted by the adrenal medulla; serves as a neurotransmitter in the brain.

48. Copyright © 2004 Allyn and Bacon 48  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.  Moclobemide: A drug that blocks the activity of MAO-A; acts as a noradrenergic agonist.  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.

49. Copyright © 2004 Allyn and Bacon 49  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. Most neurons that release norepinephrine use axonal varicosities instead of terminal buttons as a method of release.  Clonidine: A drug that stimulates presynaptic noadrenergic α 2 receptors and hence acts as an antagonist, supressing the release of NE.

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51. 51  Neurotransmitters and Neuromodulators  Monoamines Serotonin (5-HT)  Serotonin: Serotonin is an indolamine neurotransmitter; also called 5-hydroxytryptamine (5-HT); thought to play a role in the regulation of mood, the control of eating, sleep, dreaming, and arousal; also thought to be involved in the regulation of pain.

52. Copyright © 2004 Allyn and Bacon 52  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. D system:  A system of serotonergic neurons that originates in the dorsal raphe nucleus; its axonal fibers are thin, with spindle-shaped varicosities that do not appear to form synapses with other neurons.

53. Copyright © 2004 Allyn and Bacon 53  Neurotransmitters and Neuromodulators  Monoamines Serotonin (5-HT) M system:  A system of serotonergic neurons that originates in the median raphe nucleus; is a axonal fibers are thick and rounded and appear to form conventional synapses with other neurons. Fluoxetine (Prozac):  A drug that inhibits the reuptake of 5-HT.

54. Copyright © 2004 Allyn and Bacon 54  Neurotransmitters and Neuromodulators  Monoamines Serotonin (5-HT) Fenfluramine:  A drug that stimulates the release of 5-HT; used as an appetite suppressant. LSD:  Lysergic acid diethylamide  This drug produces distortions of visual perceptions.  A drug that stimulates 5-HT 2a receptors.

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57. 57  Neurotransmitters and Neuromodulators  Amino Acids  The most common amino acid transmitters are: Glutamate Gamma-amino-butyric acid (GABA) Glycine

58. Copyright © 2004 Allyn and Bacon 58  Neurotransmitters and Neuromodulators  Amino Acids  Glutamate  Glutamate: An amino acid; the most important excitatory neurotransmitter in the brain.  NMDA: A drug that serves as a noradrenergic and serotonergic agonist, also known as “ecstasy”; has excitatory and hallucinogenic effects.

59. Copyright © 2004 Allyn and Bacon 59  Neurotransmitters and Neuromodulators  Amino Acids  Glutamate  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 ionotropic glutamate receptor that controls a sodium channel; stimulated by AMPA and blocked by CNQX; the most common glutamate receptor.

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61. 61  Neurotransmitters and Neuromodulators  Amino Acids  Glutamate  Kainate receptor: An ionotropic glutamate receptor that controls a sodium channel; stimulated by kainic acid and blocked by CNQX.  Metabotropic glutamate receptor: A category of metabotropic receptors sensitive to glutamate.  AP5: A drug that blocks the glutamate binding site on NMDA receptors

62. Copyright © 2004 Allyn and Bacon 62  Neurotransmitters and Neuromodulators  Amino Acids  Glutamate  Phencyclidine (PCP): A drug that binds with the PCP binding site of the NMDA receptor and serves as an indirect antagonist of glutamate. Behavioral symptoms include altered body image, feelings of isolation and sadness, cognitive disorganization, apathy, hostility euphoria and dreamlike states.

63. Copyright © 2004 Allyn and Bacon 63  Neurotransmitters and Neuromodulators  Amino Acids  GABA  GABA: An amino acid; the most important inhibitory neurotransmitter in the brain and spinal cord.  Allygllycine: A drug that inhibits the activity of GAD and thus blocks the synthesis of GABA.

64. Copyright © 2004 Allyn and Bacon 64  Neurotransmitters and Neuromodulators  Amino Acids  GABA  Muscimol: A direct agonist for the GABA binding site on the GABA receptor.  Bicuculline: A direct antagonist for the GABA binding site on the GABA A receptor.

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66. 66  Neurotransmitters and Neuromodulators  Amino Acids  GABA  Benzodiazepine: A category of anxiolytic drugs; an indirect agonist for the GABA A receptor.  Anxiolytic: An anxiety-reducing effect.

67. Copyright © 2004 Allyn and Bacon 67  Neurotransmitters and Neuromodulators  Amino Acids  Glycine  Glycine: An amino acid; an important inhibitory neurotransmitter in the lower brain stem and spinal cord.  Strychnine: A direct antagonist for the glycine receptor.

68. Copyright © 2004 Allyn and Bacon 68  Neurotransmitters and Neuromodulators  Peptides  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.  Synthesis takes place in the soma and they are delivered to the terminal buttons by axoplasmic transport.  Most peptides appear to serve as neuromodulators, some act as neurotransmitter.

69. Copyright © 2004 Allyn and Bacon 69  Neurotransmitters and Neuromodulators  Peptides  Endogenous opioid: A class of peptides secreted by the brain that act as opiates; drugs that effect opioid receptors reduce pain.  Enkephalin: One of the endogenous opioids.  Naloxone: A drug that blocks opioid receptors.

70. Copyright © 2004 Allyn and Bacon 70  Neurotransmitters and Neuromodulators  Lipids  Cannabinoid: A lipid; an endogneous ligand for receptors that bind with THC, the active ingredient in marijuana.  Anandamide: A lipid; the endogenous ligand for receptors that bind with THC, the active ingredient of marijuana.

71. Copyright © 2004 Allyn and Bacon 71  Neurotransmitters and Neuromodulators  Lipids  Adenosine: A nucleoside; a combination of ribose and adenine; serves as a neuromodulator in the brain.  Caffeine: A drug that blocks adenosine receptors.

72. Copyright © 2004 Allyn and Bacon 72  Neurotransmitters and Neuromodulators  Soluble Gases  Nitric oxide (NO): A gas produced by cells in the nervous system; used as a means of communication between cells.  Nitric oxide synthase: The enzyme responsible for production of nitric oxide.