Week 7 - The Chemistry of Behaviour PSY1BNA PDF

latrobe.edu.au PSY1BNA Lecture 7: The Chemistry of Behaviour 1 Neurotransmitters Week 7 La Trobe University CRICOS Provider Code Number 00115M latrobe.edu.au Overview Key knowledge and understanding The different types of neurotransmitters Agonists and antagonists Neurotransmitter systems Acetylchol...

latrobe.edu.au PSY1BNA Lecture 7: The Chemistry of Behaviour 1 Neurotransmitters Week 7 La Trobe University CRICOS Provider Code Number 00115M latrobe.edu.au Overview Key knowledge and understanding The different types of neurotransmitters Agonists and antagonists Neurotransmitter systems Acetylcholine Dopamine Norepinephrine Serotonin Glutamate GABA latrobe.edu.au Readings for Neurotransmitters Recommended reading: Breedlove, S.M., & Watson, N.W. (2023). Behavioral Neuroscience (10th ed.). Sunderland, MA: Sinauer Associates, Inc. (Chapter 4; pp. 103-111). Breedlove, S.M., & Watson, N.W. (2020). Behavioral Neuroscience (9th ed.). Sunderland, MA: Sinauer Associates, Inc. (Chapter 4; pp. 97-105). Breedlove, S.M., & Watson, N.W. (2017). Behavioral Neuroscience (8th ed.). Sunderland, MA: Sinauer Associates, Inc. (Chapter 4; pp. 95-103). Part 1 Synaptic Transmission and Neurotransmitters latrobe.edu.au Introduction Neurochemistry focuses on the basic chemical composition and processes of the nervous system. Neuropharmacology is the study of compounds that selectively affect the nervous system. latrobe.edu.au Synaptic transmission latrobe.edu.au Synaptic transmission  Exogenous substances are molecules from outside our own bodies, used throughout human history to affect our physiology and behavior.  Endogenous—occurs naturally within the body. – Endogenous ligands—substances that the brain produces  When activated by a neurotransmitter, the receptors—protein molecules in the postsynaptic membrane—on neurons may – Change shape—ionotropic receptors – Alter chemical reactions in the target cell—metabotropic receptors A single neurotransmitter may interact with many different receptor subtypes in different parts of the brain—binding to fast, ionotropic receptors on some target cells and to slow, metabotropic receptors on other cells. Both types of receptors may either excite or inhibit the target cell. latrobe.edu.au Synaptic transmission latrobe.edu.au Synaptic transmission Ligands may be Agonists—mimic effects of another transmitter Antagonists—bind receptor without activating it Inverse agonists—bind to receptor and initiates opposite effect of usual transmitter Drugs that act as either agonists, antagonists or inverse agonists are known as competitive ligands (bind to the same part of receptor molecule as endogenous ligand). Noncompetitive ligands (or neuromodulators) bind to modulatory sites that are not part of the receptor complex that normally binds the transmitter. latrobe.edu.au Agonist and antagonist effects latrobe.edu.au Neurotransmitters Criteria for neurotransmitters - chemicals released onto target cells: Substance exists in presynaptic axon terminals Is synthesized in presynaptic cells Is released when action potentials reach axon terminals Receptors for the substance exist on postsynaptic membrane When experimentally applied, substance produces changes in postsynaptic cells Blocking substance release prevents changes in postsynaptic cell latrobe.edu.au Types of neurotransmitters Many chemical neurotransmitters have been identified: Amine neurotransmitters—acetylcholine, dopamine, serotonin Amino acid neurotransmitters—GABA, glutamate Peptide neurotransmitters (or neuropeptides)—short chain amino acids Gas neurotransmitters—soluble gases; nitric oxide, carbon dioxide latrobe.edu.au Examples of synaptic transmitters latrobe.edu.au Neurotransmitters Co-localization—or co-release—occurs when nerve cells contain more than one type of neurotransmitter. The most prevalent excitatory neurotransmitters in the brain are glutamate and aspartate. Glutamatergic neurotransmission uses AMPA, Kainate, and NMDA receptors Glutamate is associated with excitotoxicity, unlike gamma-aminobutyric acid (GABA), which is inhibitory. Part 2 Neurotransmitter Systems in the Brain latrobe.edu.au Neurotransmitter systems in the brain GABA receptors are divided into classes: GABAA—ionotropic, producing fast, inhibitory effects GABAB—metabotropic, slow inhibitory effects GABAC—ionotropic with a chloride channel GABA agonists, like Valium, are potent tranquilizers. latrobe.edu.au Cholinergic pathways in the brain Acetylcholine (ACh) was mapped by the enzymes involved in its synthesis. Cholinergic nerve cell bodies and projections contain ACh. Lost in Alzheimer’s disease Involved with learning and memory latrobe.edu.au Cholinergic pathways in the brain latrobe.edu.au Cholinergic pathways in the brain Two types of ACh receptors: Nicotinic—most are ionotropic and excitatory Example: Muscles use nicotinic ACh receptors (nAch)—paralysis can be induced with an antagonist, such as curare. Muscarinic—G protein-coupled (metabotropic), slower, and excitatory or inhibitory Muscarinic ACh receptors can be blocked by atropine or scopolamine to produces changes in cognition. latrobe.edu.au Monoamine neurotransmitters Two main classes of monoamine neurotransmitters: Catecholamines—dopamine, epinephrine, norepinephrine Indoleamines—melatonin, serotonin latrobe.edu.au Monoamine neurotransmitters Catecholamines Indoleamines latrobe.edu.au Dopaminergic pathways in the brain latrobe.edu.au Dopaminergic pathways in the brain Dopamine (DA) is found in neurons in The mesostriatal pathway originates in the midbrain, specifically the substantia nigra, and innervates the striatum. This pathway is important in motor control and neuronal loss is a cause of Parkinson’s disease. The mesolimbocortical DA pathway originates in the midbrain—in the ventral tegmental area (VTA)—and projects to the limbic system and cortex. DA in this pathway is involved in reward, reinforcement, and learning; abnormalities are associated with schizophrenia. latrobe.edu.au Noradrenergic pathways in the brain latrobe.edu.au Noradrenergic pathways in the brain Norepinephrine (NE) is released from two main clusters in the brainstem: Locus coeruleus (pons) Lateral tegmental system (midbrain) NE is also known as noradrenaline—cells producing it are noradrenergic. Noradrenergic fibers from the locus coeruleus project broadly. The CNS has four subtypes of NE receptors—all metabotropic. The NE systems modulate processes including mood, arousal, and sexual behavior. latrobe.edu.au Serotonergic pathways in the brain latrobe.edu.au Serotonergic pathways in the brain Serotonin (5-hydroxytryptamine, 5-HT) cell bodies are mainly found in the raphe nuclei, and their serotonergic fibers project widely. Serotonin is implicated in sleep, mood, sexual behavior, and anxiety. Antidepressants, such as Prozac, increase 5-HT activity—effects depend on which receptor subtypes are affected. latrobe.edu.au Peptide and gas NTs Peptides act as neurotransmitters at some synapses, or as hormones: Opioid peptides—mimic opiate drugs such as morphine Peptides in gut, spinal cord, or brain Pituitary hormones—oxytocin and vasopressin Nitric oxide (NO) is a gas neurotransmitter Produced in cellular locations Does not interact with membrane-bound receptors—diffuses out of and into cells Can act as a retrograde transmitter latrobe.edu.au Part 3 The Effects of Drugs latrobe.edu.au The effects of drugs depend on its dose Many drugs are ligands that act upon specific receptor molecules. Drugs may target one or a few receptor subtypes. Because receptor subtypes have different localizations and functions, drug actions can have widely varying effects. The binding affinity (or affinity) is the degree of chemical attraction between a ligand and a receptor. A drug with a high affinity for its receptor will be effective at very low doses. Neurotransmitters are low-affinity ligands, allowing them to rapidly dissociate from receptors. The efficacy (or intrinsic activity) is the ability of a bound ligand to activate the receptor. latrobe.edu.au Binding affinity and drug effectiveness latrobe.edu.au The effects of drugs depend on its dose Agonists have high efficacy; antagonists have low efficacy. Partial agonists produce a medium response regardless of dose. A dose-response curve (DRC) is a graph of the relationship between drug doses and the effects. The DRC is a tool to understand pharmacodynamics—the functional relationship between drugs and their targets. Relative potency of two drugs can be compared by their ED50 values. A drug that has comparable effects at lower doses is more potent. The is the separation between the effective dose and a toxic one. therapeutic index latrobe.edu.au The dose response curve latrobe.edu.au The dose response curve latrobe.edu.au The dose response curve latrobe.edu.au The dose response curve latrobe.edu.au The dose response curve latrobe.edu.au The effects of drugs depend on its site of action Drug tolerance can develop—successive exposures have decreasing effects. Metabolic tolerance: Organ systems become more effective at eliminating the drug. Functional tolerance: Target tissue may show altered sensitivity to the drug. Changes in numbers of receptors can alter sensitivity in the direction opposite to the drug’s effects: Neurons down-regulate in response to an agonist drug—fewer receptors available. They up-regulate in response to an antagonist. latrobe.edu.au Receptor regulation latrobe.edu.au Receptor regulation latrobe.edu.au Routes of administration and effects latrobe.edu.au Drug effects on presynaptic mechanisms latrobe.edu.au Drug effects on postsynaptic mechanisms latrobe.edu.au Concluding remarks Synaptic transmission is a complex electrochemical process Many chemical neurotransmitters have been identified Neurotransmitter systems form a complex array in the brain The effects of a drug depend on its site of action and dose Drugs affect each stage of neural conduction and synaptic transmission