 Lobes of the brain (forebrain)
 Midbrain/ Hindbrain
 Protection and Blood Supply
 Structure and Functions of a Neuron
 Synaptic Transmission
 Neurotransmitters



 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

Barlow and Durand 2005
 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
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Frontal Lobe
Temporal Lobe
Parietal Lobe
Occipital Lobe

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Located at the front of both cerebral hemispheres
Primary motor cortex
Pre-motor cortex
Broca’s Area- Motor Production of speech
Complex Functioning
Personality
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 judgement
Insight
Reasoning problem solving, abstract thinking working memory

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 Temperature
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Pain
Texture

 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.

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(http://training.seer.cancer.gov/module_anatom y/unit5_3_nerve_org1_cns.html)
 Thalamus
 filters sensory information, controls mood states and body movement associated with emotive states
 Hypothalamus
 Central control’ for pituitary gland. Regulates autonomic, emotional, endocrine and somatic function. Has a direct involvement in stress and mood states.


 regulates equilibrium, muscle tone, postural control, fine movement and coordination of voluntary muscle movement.

 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.

http://training.seer.cancer.gov/module_anatomy/unit5_3_n erve_org1_cns.html
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Meninges

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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 in the blood. Made up of tightly packed endothelial cells/capillaries making it difficult to penetrate.

 Resting potential
 Positive/negative charge
 Voltage
 Gated channels
 Sodium/ potassium pump
 Action potential
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Threshold
Depolarisation

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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
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Amines
Amino Acids
Peptides
Others

 Amines
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Dopamine
Noradrenaline
Adrenaline
Serotonin
 Amino Acids
 Glutamate and GABA
 Aspartate and glycine
 Peptides
 Cholecystrokinin
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Neuropetide Y
Vasoactive intestinal
Peptide
Substance P &
Substance K
Somatosatin
 Others
 Acetylcholine
 Histamine

Type
Other
Amino acids
Biogenic amines
Small molecule neurotransmitters
Neurotransmitter
Acetylcholine
Gamma aminobutyric acid (GABA)
Postsynaptic effect
Excitatory
Inhibitory
Glycine
Glutamate
Aspartate
Dopamine
Noradrenaline
Serotonin
Inhibitory
Excitatory
Excitatory
Excitatory
Excitatory
Excitatory

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Almost a million nerve cells in the brain contain dopamine.
Role in

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 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-
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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
Tuberoinfundibular pathway hyperprolactinemia (lactation, infertility, sexual dysfunction)
Nigrostriatal pathway extrapyramidal side effects (EPS) and tardive dyskinesia
Mesocortical pathway enhanced negative and cognitive psychotic symptoms
Mesolimbic pathway dramatic therapeutic action on positive psychotic symptoms

Type
D1, 5-like
D2, 3, 4-like
Distribution
Brain, smooth muscle
Postulated Roles
Stimulatory, role in schizophrenia?
Brain, cardiovascular system, presynaptic nerve terminals
Inhibitory, role in schizophrenia?
www.lundbeck.com.au

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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
5-HT1
5-HT2
5-HT3
5-HT4
5-HT5, 6, 7
Distribution Postulated Roles
Brain, intestinal nerves Neuronal inhibition, behavioural effects, cerebral vasoconstriction
Brain, heart, lungs,
GI system, blood vessels, platelets
Neuronal excitation, smooth muscle control, vasoconstriction, behavioural effects, depression, anxiety
Limbic system, ANS Nausea, anxiety
CNS, smooth muscle Neuronal excitation, GI
Brain Not known www.lundbeck.com.au

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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).

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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
H
2 histamine receptor
H
3 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 and to a lesser extent peripheral nervous system tissue
Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin
H
4 histamine receptor
Found primarily in the basophils and in the bone marrow. It is also found on thymus, small intestine, spleen, and colon.
Plays a role in chemotaxis.

•
•
•
•
•
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
M1
M2
M3
Distribution
Nerves
Postulated Roles
CNS excitation, gastric acid secretion
Heart, nerves, smooth muscle Cardiac inhibition, neural inhibition
Glands, smooth muscle, endothelium
Smooth, muscle contraction, vasodilation
M4
M5
?CNS?
?CNS?
NM Skeletal muscles neuromuscular junction
Not known
Not known
Neuromuscular transmission
NN Postganglionic cell body dendrites
Ganglionic transmission www.lundbeck.com.au

Scienceblogs.com
Deprexchart.gif
Norepinephrine (NE)
Found mainly in 3 areas of the brain;

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 the locus coeruleous, the pons reticular formation.
Main role;

 attention, alertness, arousal sleep/wake cycle
 regulating mood

Type Distribution
Alpha1 Brain, heart, smooth muscle
Postulated Roles
Vasoconstriction, smooth muscle control
Alpha2 Brain, pancreas, smooth Vasoconstriction, muscle presynaptic effect in GI
(relaxant)
Beta1 Heart, brain Heart rate (increase)
Beta2 Lungs, brain, skeletal muscle
Beta3 Postsynaptic effector cells
Bronchial relaxation, vasodilatation
Stimulation of effector cells www.lundbeck.com.au

 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
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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)
 CYP2D6 - Tardive dyskinesia
 Kapitany et al. (1998)
& Extra-pyramidal side-effects
 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)
D3 - Tardive dyskinesia


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Steen et al. (1997)
Kapitany et al. (1998)
Segman et al. (2000)
Ozdemir et al. (2001)
 D4 - Clozapine response
 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.

 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

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

GABA
Glutamate
Acetylcholine
Serotonin
Dopamine
Noradrenaline

Fine muscle movement, decision making, stimulates the hypothalamus to release hormones
Stimulates the ANS – Fright & Flight
=
Learning & Memory sleep regulation, hunger, mood states, pain perception, aggression and sexual behaviour

Dopamine
Acetylcholine

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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