Class is Cancelled! Tuesday, Oct 16th

1. Class is Cancelled! Tuesday, Oct 16th Midterm #1 – Thursday, Oct. 4th

2. Assignment • Due March 5th • Sign-up sheet for “lab component” located outside my office (Sn 1061) • Sign-up for 1 hour slot – 4 people/time slot • Monday, Feb 11 - Friday, Feb 15

3. Major Division Ventricle Subdivision Principle Structures Cerebral cortex Telencephalon Lateral Basal ganglia Limbic System Forebrain Thalamus Anatomy Basics Diencephalon Third Hypothalamus Cerebral aqueduct Tectum Tegmentum Mesencephalon Midbrain Cerebellum Metencephalon Fourth Hindbrain Pons Myelencephalon Medulla oblongata

4. Mind and Brain Psychopharmacology Chapter 4

5. Chapter Preview • Principles of Psychopharmacology • Sites of Drug Action • Neurotransmitters and Neuromodulators

6. Introduction • Psychopharmacology • The study of the effects of drugs on the nervous system and 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 drug interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells.

7. Principles of Psychopharmacology • Pharmacokinetics • The process by which drugs are absorbed, distributed within the body, metabolized, and excreted.

8. Principles of Psychopharmacology • Routes of Administration • Intravenous (IV) Injection – injection of a substance directly into a vein. • Drug enters bloodstream immediately and reaches the brain in seconds

9. Principles of Psychopharmacology • Routes of Administration • Intraperitoneal (IP) Injection – injection of a substance into the peritoneal cavity, the space that surrounds the stomach, intestines, liver, and other abdominal organs. • Most common route for small laboratory animals

10. Principles of Psychopharmacology • Routes of Administration • Intramuscular (IM) Injection – injection of a substance into a muscle.

11. Principles of Psychopharmacology • Routes of Administration • Subcutaneous (SC) Injection – injection of a substance into the space beneath the skin.

12. Principles of Psychopharmacology • Routes of Administration • Oral Administration – administration of a substance into the mouth so that it is swallowed. • Sublingual Administration – administration of a substance by placing it beneath the tongue.

13. Principles of Psychopharmacology • Routes of Administration • Intrarectal Administration – administration of a substance into the rectum. • Inhalation – administration of a vaporous substance into the lungs. • Topical Administration – administration of a substance directly onto the skin or mucous membrane. • Insufflation – sniffing drugs; contacts mucous membranes of the nasal passages; sniffing not same as inhalation!

14. Principles of Psychopharmacology • Routes of Administration • Intracerebral Administration – administration of a substance directly into the brain. • Intracerebroventricular (ICV) Administration – administration of a substance into one of the cerebral ventricles.

15. Principles of Psychopharmacology • Distribution of Drugs Within the Body • Lipid Solubility – ease with drug molecules are soluble in fat. • Heroin more lipid soluble than morphine so gets to brain faster; more intense ”rush” • Depot Binding – binding of a drug with various tissues of the body or with proteins in the blood. • If drug bound to depot cannot reach site of action • Albumin – a protein found in the blood; serves to transport free fatty acids and can bind with some lipid-soluble drugs.

16. Depot Binding with Blood Albumin Protein Figure 4.2

17. Principles of Psychopharmacology • Inactivation and Excretion • Enzymes deactivate drugs (e.g., liver). • Drugs are eventually excreted (e.g., kidneys).

18. Principles of Psychopharmacology • Drug Effectiveness • Dose-Response Curve – a graph of the magnitude of an effect of a drug as a function of the amount of drug administered.

19. Figure 4.3 A Dose-Response Curve Usually defined as mg of drug/Kg of body weight

20. Principles of Psychopharmacology • Drug Effectiveness • Sites of actions • Affinity – the readiness with which two molecules join together • Many drugs have more than one effect, which should be taken into consideration when determining the effect dose for treatment.

21. Figure 4.4 Dose-Response Curves for Morphine

22. Principles of Psychopharmacology • 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. • If toxic dose is 5 times higher than the effective dose then the TI = 5 • The lower the TI, the more care must be taken in prescribing the drug

23. Principles of Psychopharmacology • Effects of Repeated Administration • Tolerance – a decrease in the effectiveness of a drug that is administered repeatedly. • 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. • Sensitization – an increase in the effectiveness of a drug that is administered repeatedly.

24. Principles of Psychopharmacology • Placebo Effects • An inert substance that is given to an organism in lieu of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug.

25. Sites of Drug Action • Most drugs that affect behavior affect synaptic transmission • Two categories: • Antagonists – Drugs that oppose or inhibit the effects of a particular neurotransmitter on the postsynaptic cell. • Agonists – Drugs that facilitate the effects of a particular neurotransmitter on the postsynaptic cell.

26. Review of steps in synaptic transmission (Chapter 2) • Neurotransmitters are synthesized and stored in synaptic vesicles • Vesicles travel to presynaptic membrane and dock • Axon fires and voltage-dependent calcium channels open allowing calcium ions to enter • Calcium ions interact with docking proteins causing release of neurotransmitter into synaptic cleft • Neurotransmitter binds to postsynaptic receptor, ion channels open, PSPs produced • Effects of neurotransmitter kept brief by reuptake or enzymatic degradation • Stimulation of autoreceptors regulates synthesis and release of neurotransmitter

27. Sites of Drug Action • Act on Neurotransmitters • Enzymes control the synthesis of a neurotransmitter from its precursors. • Rate of synthesis and release can be increased by administering the precursor • The precursor serves as an agonist (step 1 in Figure 4.5) • If a drug inactivates the enzymes it prevents the neurotransmitter from being produced • It serves as an antagonist (step 2 in Figure 4.5)

28. Figure 4.5 Drug Affects on Synaptic Transmission

29. Sites of Drug Action • Effects on Storage and Release of Neurotransmitters • Drugs may exert their agonistic or antagonistic effects by influencing the storage and release of neurotransmitters. • Some drugs can prevent the storage of neurotransmitter in the vesicles – antagonists (step 3 in Figure 4.5) • Some drugs can also prevent the release of neurotransmitters by deactivating proteins that cause synaptic vesicles to fuse with presynaptic membrane (step 5 in Figure 4.5) • Other drugs act as agonists by triggering the release of neurotransmitter (step 4)

30. Figure 4.5 Drug Affects on Synaptic Transmission

31. Sites of Drug Action • Effects on Receptors • Drugs may exert their agonistic or antagonistic effects by influencing receptors. • Direct Agonist – a drug that binds with and activates a receptor; mimics the effects of a neurotransmitter (step 6 in Figure 4.5). • Direct Antagonist – a drug that binds with a receptor but does not activate it; prevents the natural ligand from binding with the receptor; also called receptor blocker (step 7 in Figure 4.5).

32. Figure 4.5 Drug Affects on Synaptic Transmission

33. Sites of Drug Action • Noncompetitive Binding – binding of a drug to a site on a receptor; does not interfere with the binding site for the principal ligand. • 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 site for 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 for the principal ligand.

34. Figure 4.6 Drug Actions at Binding Sites

35. Sites of Drug Action • Autoreceptors – regulate the amount of neurotransmitter released • Drugs that activate these receptors serve as antagonists, decreasing the amount of neurotransmitter released (step 8 in Figure 4.5) • Drugs that block the presynaptic autoreceptors increase the release of neurotransmitter (step 9 in Figure 4.5)

36. Figure 4.5 Drug Affects on Synaptic Transmission

37. Sites of Drug Action • Some terminal buttons form axoaxonic synpases • 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.

38. Figure 4.7 Presynaptic Heteroreceptors

39. Figure 4.8 Dendritic Autoreceptors

40. Sites of Drug Action • Effects on Reuptake or Destruction of Neurotransmitters • Drugs can attach to transporter molecules responsible for reuptake and inactivate them • Drugs can bind with the enzyme that normally destroys the neurotransmitter and prevent it from working • Both types of drugs prolong the presence the neurotransmitter in the synaptic cleft – agonists (steps 10 and 11 in Figure 4.5).

41. Figure 4.5 Drug Affects on Synaptic Transmission