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

4. Copyright © Allyn & Bacon 2004 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 © Allyn & Bacon 2004 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 © Allyn & Bacon 2004 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.

7. Copyright © Allyn & Bacon 2004 7  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.

8. Copyright © Allyn & Bacon 2004 8  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.

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11. 11  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.

12. Copyright © Allyn & Bacon 2004 12  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.

13. Copyright © Allyn & Bacon 2004 13  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.

14. Copyright © Allyn & Bacon 2004 14  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.

15. Copyright © Allyn & Bacon 2004 15  Sites of Drug Action  Effects on Receptors  Direct agonist: A drug that binds with an 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.

16. Copyright © Allyn & Bacon 2004 16  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.

17. Copyright © Allyn & Bacon 2004 17  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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20. 20  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.

21. Copyright © Allyn & Bacon 2004 21  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.

22. Copyright © Allyn & Bacon 2004 22  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.

23. Copyright © Allyn & Bacon 2004 23  Neurotransmitters and Neuromodulators  Monoamines  Catecholamines Dopamine (DA) Norepinephrine (NE) Epinephrine  Indolamines Serotonin (5-HT)

24. Copyright © Allyn & Bacon 2004 24  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)

25. Copyright © Allyn & Bacon 2004 25  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.

26. Copyright © Allyn & Bacon 2004 26  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.

27. Copyright © Allyn & Bacon 2004 27  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.

28. Copyright © Allyn & Bacon 2004 28  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.

29. Copyright © Allyn & Bacon 2004 29  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.

30. Copyright © Allyn & Bacon 2004 30  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.

31. Copyright © Allyn & Bacon 2004 31  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.

32. Copyright © Allyn & Bacon 2004 32  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.

33. Copyright © Allyn & Bacon 2004 33  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.

34. Copyright © Allyn & Bacon 2004 34  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.

35. Copyright © Allyn & Bacon 2004 35  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.

36. Copyright © Allyn & Bacon 2004 36  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.

37. Copyright © Allyn & Bacon 2004 37  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.  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.

38. Copyright © Allyn & Bacon 2004 38  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.

39. Copyright © Allyn & Bacon 2004 39  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.

40. Copyright © Allyn & Bacon 2004 40  Neurotransmitters and Neuromodulators  Monoamines Serotonin (5-HT) Fluoxetine (Prozac):  A drug that inhibits the reuptake of 5-HT.

41. Copyright © Allyn & Bacon 2004 41  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.

42. Copyright © Allyn & Bacon 2004 42  Neurotransmitters and Neuromodulators  Amino Acids  The most common amino acid transmitters are: Glutamate Gamma-amino-butyric acid (GABA) Glycine

43. Copyright © Allyn & Bacon 2004 43  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

44. Copyright © Allyn & Bacon 2004 44  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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46. 46  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

47. Copyright © Allyn & Bacon 2004 47  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.

48. Copyright © Allyn & Bacon 2004 48  Neurotransmitters and Neuromodulators  Amino Acids  GABA  GABA: An amino acid; the most important inhibitory neurotransmitter in the brain and spinal cord.

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50. 50  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.

51. Copyright © Allyn & Bacon 2004 51  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.

52. Copyright © Allyn & Bacon 2004 52  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.

53. Copyright © Allyn & Bacon 2004 53  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.

54. Copyright © Allyn & Bacon 2004 54  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.

55. Copyright © Allyn & Bacon 2004 55  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.

56. Copyright © Allyn & Bacon 2004 56  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.