HUMAN PSYCHOPHARMACOLOGY Dr David Sutherland

1. HUMAN PSYCHOPHARMACOLOGYDr David Sutherland LECTURE 1

2. Psychopharmacology psychopharmacology = the study of the effects of drugs on cognition, mood & behaviour drugs can only have these �psychoactive� properties if they interact with naturally occurring (�endogenous�) chemical systems in the brain drugs are powerful tools (or �probes�) for learning about the functions of these systems

3. psychopharmacology aims to improve our understanding of the relationship between brain chemistry and function, both normal and abnormal psychopharmacology can offer treatments for medical conditions (Alzheimer�s, schizophrenia, depression, etc.) may also offer the possibility of enhancing normal functioning

4. Basic neuroscience:

9. Neurotransmitter (NT) systems project from lower brain areas (e.g. brainstem nuclei) to higher areas (forebrain)

10. these systems can send excitatory signals - increasing activity in target areas or inhibitory signals - reducing activity in target areas

11. different neural systems can be identified on the basis of different neurotransmitters (NTs) used - acetylcholine (= cholinergic system) noradrenaline (= noradrenergic system) dopamine (= dopaminergic system) serotonin (= serotonergic system) etc. more than 100 different NTs have been identified in humans we are only going to cover a few of these�

12. The neuron & synapse

13. Nerve impulse (action potential) arrives at axon terminal This leads to release of NT into synaptic cleft NT binds to post-synaptic receptor site Post-synaptic neuron is excited or inhibited NT is deactivated and/or taken back into terminal

14. NTs bind to post-synaptic receptors can have an excitatory effect, making receiving neuron more likely to produce an action potential or can have an inhibitory effect, making receiving neuron less likely to produce an action potential depends on receptor type

15. Synapse structures

16. Processes in neurotransmitter action

17. 2 mechanisms of NT deactivation: reuptake & enzymatic breakdown

19. Neurotransmission neurotransmitters bind to post-synaptic receptors on dendrite of receiving neuron this triggers changes in the permeability of the post-synaptic neuron membrane, by affecting the opening and closing of ion channels this can have an excitatory effect (making receiving neuron more likely to produce an action potential), or an inhibitory effect (making receiving neuron less likely to produce an action potential)

20. Receptors & ion channels

21. Ion channels

22. Lock & Key Model NT binds to receptor NT = key receptor = lock receptor shape determines different receptor subtypes (can be excitatory or inhibitory)

23. same NT can bind to different receptors different part of NT fits different receptors same NT can be excitatory or inhibitory, depending on receptor

25. Agonist & antagonist drugs

26. agonists � mimic or enhance the effect of a particular neurotransmitter antagonists � block or reduce the effect of a particular neurotransmitter

27. Agonistic & antagonistic drug effects

28. Therapeutic use of agonist & antagonist drugs: Agonists - used to treat conditions involving underactivity of neurotransmitters e.g. dopamine agonists are used in treatment of Parkinson�s disease Antagonists - used to treat conditions involving overactivity of neurotransmitters e.g. dopamine antagonists are used in treatment of schizophrenia

29. Measuring drug effects task performance � simple reaction time, choice reaction time, vigilance, memory, problem solving, etc. self-report mood � alertness, happiness, anxiety, etc. observer-rated behaviour � hyperactivity, aggressiveness, etc.

32. Methodology randomized placebo-controlled trials - compare effects of drug with non-psychoactive (but otherwise identical) placebo treatment participants are randomly assigned to groups �blind� or �double-blind� to control for expectancy effects blind = subjects do not know whether they have been given drug or placebo double-blind = neither subjects nor experimenter knows, until after the study is completed; this is the �gold standard� for psychopharmacological research

33. Placebo effects in randomized, double-blind, placebo-controlled clinical trials of approved medications(Khan et al 2005, Psychological Medicine 35, 743-749) white bar = placebo black bar = drug n = number of trials OCD = obsessive-compulsive disorder GAD = generalized anxiety disorder PTSD = post-traumatic stress disorder

34. SUMMARY (1): Neurotransmitters neurotransmitters are synthesized in neurons by enzymes they are stored in vesicles, until released they are released into the synaptic cleft in response to an incoming action potential they diffuse across the synaptic cleft and bind to postsynaptic receptors can have either an excitatory or an inhibitory effect on the postsynaptic neuron, depending on the receptors they are rapidly cleared from the synaptic cleft by reuptake and/or enzymatic breakdown

36. SUMMARY (2): Drugs psychoactive drugs interact with neuro-transmitter (NT) systems they can influence NT synthesis, storage, release, receptor interactions, and/or reuptake and breakdown they can have agonistic effects, where they mimic or enhance the effects of a NT they can have antagonistic effects, where they block or reduce the effects of a NT

37. The exam Lectures 2-6 will all include a short list of �Learning Outcomes� � these will help you to focus on the key issues that will be the basis of exam questions You will also be given readings that relate to Learning Outcomes

38. Learning Outcomes (& exam Qs) focus on � understanding the role of a particular neuro-transmitter (NT) in human cognition, mood & behaviour the involvement of the NT in abnormal psychological functioning how particular classes of drugs interact with NT - and how they affect cognitive functions, mood & behaviour

39. You will not need to learn the names of all the drugs mentioned in lectures � just the names of a few classes of drugs You will not need to have a detailed knowledge of the brain areas where a particular NT is found You will not need to have a detailed knowledge of the chemical processes that occur in the brain (this is a course in psychopharmacology, not biochemistry)

40. Recommended textbooks (Routledge �7.99) (Wiley �24.99)