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Neuropharmacology Effects of drugs on the nervous system Brain is seat of integration of nervous activity and consciousness Drug effects on CNS affects.

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Presentation on theme: "Neuropharmacology Effects of drugs on the nervous system Brain is seat of integration of nervous activity and consciousness Drug effects on CNS affects."— Presentation transcript:

1 Neuropharmacology Effects of drugs on the nervous system Brain is seat of integration of nervous activity and consciousness Drug effects on CNS affects behaviour, moods, cognitive ability, motor activity, sensory interpretation Psychopharmacology

2 The Grand Scheme CNS Structure and Function Methods of research in Behavioural Psychopharmacology Neurotransmitters and the CNS Neurodegenerative disorders

3 And then…………. Drug dependance and addiction Alcohol, CNS stimulators, cannabinoids, opiates Anaesthetics Affective disorders Anxiety disorders Schizophrenia

4 Psychoactive drugs Found throughout recorded history Opium poppy Neolithic burial sites Alcohol Ancient Mesopotamia – laws to control drinking Peyote cactus (mescaline) Native Americans Amanita mushroom Vikings

5 Curative or Medicinal Effects Coca leaves (cocaine) S.American silver mines – increase mental and physical vigilance in low PO 2 environment Tea (caffeine) General tonic for the sages of Ancient China Indian snake root (rauwolfia serpenina) Treatment for manic excitement, hallucinations, delusion Reserpine – depletes dopamine stores

6 Psychoactive Drugs: 1000s of drugs – only a few main CLASSES

7 Common Mechanisms CNS stimulants: eg amphetamine (amine), cocaine (alkaloid) Alertness , faster behavioural responses Stimulate release of dopamine, inhibits its inactivation Most CNS stimulants boost dopamine and/or adrenaline

8 CNS depressants Eg alcohol, barbiturates Feelings of sleepiness, impaired psychomotor functions CNS depressants affect the GABA (  amino butyric acid) receptor GABA-ergic drugs inhibit neuronal activity

9 Drugs +ve and –ve effects Alcohol (aggression, antisocial behaviour, criminal behaviour) Cocaine (aggression, suspicion) Antidepressants (drowsiness, dry mouth) Antipsychotics (drowsiness, dry mouth etc) Tolerance (adaptive change in CNS) Dependance (no benefit; only satisfy craving etc)

10 Divisions of the Nervous System Rest and digestion Fight and flight

11 Sensory afferent neurons Sensory (afferent: “towards”) Chemoreceptors Mechanoreceptors Nociceptors Photoreceptors Thermoreceptors

12 Polysynaptic Reflex Effectors: Muscles Glands Conscious or unconscious PROCESSING

13 Reaction Times vary with complexity of task 1ms delay for each synapse Time between input and output increase with the number of synapses Monosynaptic “knee jerk” takes around 30ms Reaction time task: 200ms Choice reaction time task: >450ms Reaction time  Information processing Sensitive to drug effects CNS stimulants reduce reaction time CNS depressant drugs retard reaction time

14 The Brain (Cerebral cortex)

15 Cerebrospinal Fluid (CSF)

16 CSF-filled subarachnoid space

17 Typical vs Brain Capillaries

18 Blood Brain Barrier –selectively permeable (not impermeable) Typical capillaries Intercellular clefts Fenestrations Pinocytotic vesicles Brain capillaries IC clefts closed (tight junctions) Fenestrations absent Pinocytotic vesicles rare “Glial feet” extensions of astrocytes surround capillaries

19 Blood-Brain barrier not complete Area Postrema (or CTZ – chemical trigger zone) Medulla of brain stem “vomiting centre” Median eminence of the hypothalamus Hypothalamic neurotransmitters  anterior pituitary

20 Limited permeability and drug action Physostigmine readily crosses barrier Useful for treating intoxication from pesticides Increases availability of acetylcholine Neostigmine is excluded from brain increases Ach only peripherally Neostigmine can treat myasthenia gravis without CNS side effects, but not pesticide induced intoxication

21 Regions of the Brain

22 Telencephalon Cerebral cortex Limbic system Moods, emotions, learning,memory Basal ganglia Voluntary movement

23 The Limbic System

24 Basal Ganglia: dopamine (corpus striatum) (mesencephalon)

25

26 Metencephalon and myelencephalon (medulla) of hind brain Cerebellum Pons/medulla = brainstem Vasomotor, cardiac centre, respiratory centre, vomiting, cough Brainstem death (o.d. CNS depressants)

27 Ascending Reticular Activating System ARAS – fibre bundle runs through core of brainstem into thalamus Maintains arousal Sedative-hypnotic drugs reduce basic ARAS activity – sleepiness Antipsychotic drugs (eg chlorpromazine) reduce sensory and cortical input to ARAS Person awake, but less arousable; either by environmental events or their own thoughts/feelings

28 Neurones 100 trillion (10 12 ) Each neuron connects to 1000 – others 1g cortex = 10 9 synapses Lost at per day

29 The Neurone Soma (cell body Dendrites (and dendritic spines) Receive signals from other cells via a gap called the synapse Axons Single tubular extension conducts electrical signal to terminal boutons

30 Formation of Myelin Sheath CNS

31 Axonal Transport KINESIN DYNEIN

32 Action Potential “All or Nothing”

33 The Neural Code Discharge frequency dependant upon stimulus intensity Action potential must be “re-set” before another can be triggered Refractory period

34 The Resting Potential Differential permeability Electrostatic gradient -70mV (inside vs outside)

35 Saltatory Conduction

36

37 Summation of IPSP/EPSP

38 THE SYNAPSE presynaptic postsynaptic


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