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Lobes of the brain (forebrain) Midbrain/ Hindbrain Protection and Blood Supply Structure and Functions of a Neuron Synaptic Transmission Neurotransmitters The central nervous system consists of the brain and the spinal cord and is responsible for our basic functions, personality and behaviour. Cerebrum and Cerebral cortex Left and Right Hemispheres Left hemisphere for most people is the dominant hemisphere- responsible for production of language, mathematical ability, problem solving, logic Right hemisphere thought to be responsible for creativity and spatial ability Most complex organ in the body Weighs 1,300 grams Contains billions of neural networks that interact to create human behaviour The major sections of the cerebral hemispheres are divided up into lobes. The lobes are named after the bones of the skull that overlie them Frontal Lobe Temporal Lobe Parietal Lobe Barlow and Durand 2005 Occipital Lobe Located at the front of both cerebral hemispheres Primary motor cortex Pre-motor cortex Broca’s Area- Motor Production of speech Complex Functioning Personality judgement Insight Reasoning problem solving, abstract thinking working memory Located behind the temporal lobe Sensory information Temperature Pain Texture Spatial orientation Perception Recognising object by touch Links visual and sensory information together Neglect Auditory information Higher order visual information Complex memory Memory of faces Comprehension of language (Wernicke’s area) http://www.nidcd.nih.gov/health/voice/aphasia.asp) Rearmost portion of the brain Visual processing area Corpus Callosum- Fibre bundle in the brain that connects the two hemispheres together. Hypothalamus Thalamus Cerebellum Pons Medulla Oblongata Reticular formation Basal Ganglia Substantia Nigra Amygdala Hippocampus Thalamus filters sensory information, controls mood states and body movement associated with emotive states (http://training.seer.cancer.gov/module_anatom y/unit5_3_nerve_org1_cns.html) Hypothalamus Central control’ for pituitary gland. Regulates autonomic, emotional, endocrine and somatic function. Has a direct involvement in stress and mood states. Cerebellum regulates equilibrium, muscle tone, postural control, fine movement and coordination of voluntary muscle movement. Pons Relay station between cerebrum and cerebellum www.deryckthake.com/psychim ages/hindbrain. Medulla oblongata Conscious control of skeletal muscles, balance, co-ordination regulating sound impulses in the inner ear, regulation of automatic responses such as heart rate, swallowing, vomiting, coughing and sneezing Reticular Formation Important in arousal and maintaining consciousness, alertness attention and Reticular Activating System which controls all cyclic functions i.e. respiration, circadian rhythm. Basal Ganglia Control of muscle tone, activity, posture, large muscle movements and inhibit unwanted muscle movements. Substatia Nigra Produces dopamine, is connected to the basal ganglia – EPSE’s Amygdala mediates and controls major affective mood states such as friendship , love, affection, fear, rage and aggression. Hippocampus Memory, particularly the ability to turn short term memory into long term memory. Alzheimer's disease. Meninges Dura mater Arachnoid Mater Subarachnoid space Pia mater CSF 2 main functions; shock absorption and mediation of blood's vessels and brain tissue in exchange of nutrients. Circle of Willis carotid arteries and baliser arteries Blood Brain Barrier Protect the brain from chemicals http://training.seer.cancer.gov/module_anatomy/unit5_3_n erve_org1_cns.html in the blood. Made up of tightly packed endothelial cells/capillaries making it difficult to penetrate. Resting Potential Resting potential Positive/negative charge Voltage Gated channels Sodium/ potassium pump Action potential Threshold Depolarisation Action Potential Calcium ion channels stimulate the release of neurotransmitters Vesicles fuse to the cell membrane and release into the synapse Lock and key effect Reuptake of neurotransmitters into the cell or broken down by enzymes in the synaptic cleft There are two kinds of neurotransmitters – INHIBITORY and EXCITATORY. stimulate the brain calm the brain Neurotransmitter is a chemical Its released from the synaptic cleft Another term for neurotransmitter is a ligand Three main groups of neurotransmitters Amines Amino Acids Peptides Others Amines Dopamine Noradrenaline Adrenaline Serotonin Amino Acids Glutamate and GABA Aspartate and glycine Peptides Cholecystrokinin Neuropetide Y Vasoactive intestinal Peptide Substance P & Substance K Somatosatin Others Acetylcholine Histamine Small molecule neurotransmitters Type Neurotransmitter Postsynaptic effect Other Acetylcholine Excitatory Amino acids Gamma aminobutyric acid (GABA) Inhibitory Glycine Inhibitory Glutamate Excitatory Aspartate Excitatory Dopamine Excitatory Noradrenaline Excitatory Serotonin Excitatory Biogenic amines Neural Communication Almost a million nerve cells in the brain contain dopamine. Role in complex movement cognition motor control emotional responses such as euphoria or pleasure. Newer antipsychotic medication focus on particular dopaminergic pathways in the brain. Lessening EPSE’s. The dopamine hypothesis of psychosis – overactivity of dopamine neurons in the mesolimbic pathway of the brain may mediate the positive symptoms of psychosis Mesolimbic pathway responsible for pleasure, effects of drugs and alcohol and hallucinations and delusions Five subtypes – D2 most important in terms of psychosis Blockade of mesolimbic receptors leads to reduced psychotic symptoms Blockade of the mesocortical pathway leads to increased negative symptoms Dopamine and acetylcholine have a reciprocal relationship Blockade of dopamine receptors increases the activity of acetylcholine Over activity of acetylcholine causes EPSE Blockade of dopamine causes movement disorders in the nigostriatal pathway Long term blockade causes “upregulation” and leads to Tardive Dyskinesia D2 Nigrostriatal pathway extrapyramidal side effects (EPS) and tardive dyskinesia Mesocortical pathway enhanced negative and cognitive psychotic symptoms Tuberoinfundibular pathway hyperprolactinemia (lactation, infertility, sexual dysfunction) Mesolimbic pathway dramatic therapeutic action on positive psychotic symptoms Type Distribution Postulated Roles D1, 5-like Brain, smooth muscle Stimulatory, role in schizophrenia? D2, 3, 4-like Brain, Inhibitory, role in cardiovascular schizophrenia? system, presynaptic nerve terminals www.lundbeck.com.au Believed to be one of the great influences on behaviour. Complex neurotransmitter. Surprisingly only 2% of serotonin is found in CNS. Roles include Vasoconstriction, gastrointestinal regulation. Low serotonin associated with aggression, suicide, impulsive eating, anxiety and low mood. Regulates general activity of the CNS, particularly sleep. Delusions, hallucinations and some of the negative symptoms of schizophrenia. www.rodensor.com/images/site_gra phics/Dopamineseratonin Type Distribution Postulated Roles 5-HT1 Brain, intestinal nerves Neuronal inhibition, behavioural effects, cerebral vasoconstriction 5-HT2 Brain, heart, lungs, Neuronal excitation, smooth muscle control, vasoconstriction, behavioural GI system, blood effects, depression, anxiety vessels, platelets 5-HT3 Limbic system, ANS Nausea, anxiety 5-HT4 CNS, smooth muscle Neuronal excitation, GI 5-HT5, 6, 7 Brain Not known www.lundbeck.com.au Glutamate is found in all cells of the body control the opening of ion channels that allow calcium to pass into nerve cells producing impulses Blocking of glutamate receptors produces psychotic symptoms ( eg. By PCP) schizophrenic like symptoms Over exposure of neurons to glutamate cause cell death seen in stroke and Huntington’s disease (PN). Inhibitory and its pathways are only found within the CNS. control excitatory neurotransmitters in the brain and controlling spinal and cerebral reflexes. anxiety disorders decreased GABA can lead to seizure activity Benzodiazepines and barbiturates sedative medication act on GABA Benzo.org.au Found in the posterior hypothalamus. Believed to be involved in the regulation of the sleeping and waking states. Histaminergic cells fire rapidly during waking and slowly during periods of relaxation and tiredness. Cease transmission during REM and non-REM sleep Type H1 Histamine Receptor H2 histamine receptor H3 histamine receptor H4 histamine receptor Location Found on smooth muscle, endothelium, and CNS tissue Located on parietal cells and vascular smooth muscle cells Function bronchoconstriction, bronchial smooth muscle contraction, separation of endothelial cells (responsible for hives), pain and itching due to insect stings; receptors involved in allergic rhinitis symptoms motion sickness; sleep regulation. vasodilatation. stimulate gastric acid secretion Found on central nervous system Decreased neurotransmitter release: and to a lesser extent peripheral histamine, acetylcholine, nervous system tissue norepinephrine, serotonin Found primarily in the basophils and in the bone marrow. It is also Plays a role in chemotaxis. found on thymus, small intestine, spleen, and colon. • Cholinergic pathways • thought to be involved in cognition (esp. memory) and our sleep/wake cycle • parasympathetic nervous system regulating bodily functions such as heart rate, digestion, secretion of saliva and bladder function • Alzheimer’s disease and myathesia gravis (weakness of skeletal muscles) • Anti-cholinergic effects Type Distribution M1 Nerves M2 M3 M4 M5 NM NN Postulated Roles CNS excitation, gastric acid secretion Heart, nerves, smooth muscle Cardiac inhibition, neural inhibition Glands, smooth muscle, Smooth, muscle contraction, endothelium vasodilation ?CNS? Not known ?CNS? Not known Skeletal muscles Neuromuscular transmission neuromuscular junction Postganglionic cell body dendrites Ganglionic transmission www.lundbeck.com.au Norepinephrine (NE) Found mainly in 3 areas of the brain; the locus coeruleous, the pons reticular formation. Main role; Deprexchart.gif Scienceblogs.com attention, alertness, arousal sleep/wake cycle regulating mood Type Alpha1 Distribution Brain, heart, smooth muscle Alpha2 Brain, pancreas, smooth Vasoconstriction, muscle presynaptic effect in GI (relaxant) Heart, brain Heart rate (increase) Beta1 Postulated Roles Vasoconstriction, smooth muscle control Beta2 Lungs, brain, skeletal muscle Bronchial relaxation, vasodilatation Beta3 Postsynaptic effector cells Stimulation of effector cells www.lundbeck.com.au The 3 Neurotransmitters song Pharmacogenetics The variability in response to modern multi-target drugs suggests a complex trait in which several genes may play a part in the bodies response to drugs. Reported associations between polymorphic receptors for metabolic enzymes and treatment response confirm this hypothesis These results can be taken as evidence of the genomic influence in drug response 5-HTs, 5-HTT, H2 - Clozapine response prediction Arranz et al. (2000) 5-HT6 - Clozapine response Yu et al. (1999) 5-HTT - Response to SSRIs Smeraldi et al. (1998) Kim et al. (2000) APOE, PS1 and PS2 - Alzheimer’s disease treatment response Cacabelos et al. (2000) CYP1A2 - Movement disorders Basile et al. (2000) D3 - Tardive dyskinesia Steen et al. (1997) Kapitany et al. (1998) CYP2D6 - Tardive dyskinesia Kapitany et al. (1998) Segman et al. (2000) & Extra-pyramidal side-effects D4 - Clozapine response Scordo et al. (2000) CYP2C19 - Mephenytoin blood levels Ferguson et al. (1998) D2 Short-term neuroleptic response Malhotra et al. (1999) Schafer et al. (2001) D3 - Clozapine response Scharfetter et al. (1998) Ozdemir et al. (2001) Shaikh et al. (1993) 5-HT2A - Clozapine response Arranz et al. (1995, 1998b) 5-HT2C - Clozapine response Sodhi et al. (1995) Tardive dyskinesia Segman et al. (2000) The study of the movement of a drug through the body Absorption Distribution Metabolism Elimination Absorption The rate at which a drug gets out of the G.I tract and into the blood stream Distribution Process of drug molecules leaving the blood stream to reach tissues and organs General body capillaries allow drug molecules to pass freely into the surrounding tissue. Brain capillaries have a dense walled structure & are surrounded by glial cells (lipid). This prevents many drug molecules from entering the surrounding tissue. Glial cells Capillary wall Metabolism: Detoxification or breakdown. Enzymes (Cytochrome P450) in liver cells transform drug from fat soluble to water soluble. Elimination: removal of drug from body. Most via kidney’s, lungs & G.I. Tract (small amounts) nature.com Pharmacokinetics clip Drug receptor interaction: drug concentrated at the site of action. Effect (body responses): Therapeutic effects, intoxication & side effects. The effect will vary depending on age, gender & health of person, plus the route, frequency of use, duration of use and the environment in which the drug is consumed. Blockade of receptors Receptor sensitivity changes Reuptake inhibition Interference with storage vesicles Pre-curser chain interference Synaptic enzyme inhibition Second messenger cascade Neurotransmitter Re-uptake pump Receptor Axon Dendrite Synapse Presynaptic storage vesicles Acetylcholine GABA Serotonin Dopamine Glutamate Noradrenaline Fine muscle movement, decision making, stimulates the hypothalamus to release hormones Stimulates the ANS – Fright & Flight Dopamine Noradrenaline = Serotonin sleep regulation, hunger, mood states, pain perception, aggression and sexual behaviour Acetylcholine Learning & Memory Acetylcholine Noradrenaline & Serotonin Glutamate, Noradrenaline Dopamine Acetylcholine Dopamine Acetylcholine Acetylcholine Dopamine Dopamine Norepinephrine Acetylcholine Serotonin Boyd (2002). Psychiatric Nursing , contemporary practice .Lippincott, USA Rosenweig, Breedlove and Leiman (2002) Biological Psychology: an introduction to cognitive, behavioural and clinical neuroscience 3rd Edition.Sineur Associates , Inc USA. Stuart and Laraia (2005) Prinicples and Practice of Psychiatric Nursing. Mosby, USA. Barlow and Durand (2005). Abnormal Psychology, and intergrated approach.Thompson/Wadsworth, Australia. Leonard BE (1997). Fundamentals in Psychopharmacology. 2nd ed. Chichester: Wiley & Sons. Purves DE, Augustine GJ, Fitzpatrick D, et al. (eds). Neuroscience. Sunderland, MA: Sinauer Associates, Inc; 1997. Lundbeck Institute, www.brainexplorer.com Blakemore & Frith (2005). The Learning Brain. Blackwell Publishing Begley (2005). The blood brain Barrier. Gauchers News May 2005c Staddon S, Arranz MJ, Mancama D, Mata I, Kerwin RW (2002) Clinical applications of pharmacogenetics in psychiatry, Psychopharmacology 162: 18–23