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Chapter 4-5

HSCI180 CH4-5 Nervous System/Actions of drugs.docx

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Health Sciences
HSCI 180
Julian Somers

CHAPTER 4–NervousSystem Nervous System 1. PERIPHERAL NERVOUS SYSTEM Contains all the neural structures that lie outside of the brain and spinal cord.  Somatic Nervous System (external environment) o Carry sensory information to brain (vision, hearing, skin, joints) o Carry motor info from brain to control voluntary movements (muscles) o Neurotransmitter is acetylcholine, at neuromuscular junctions  Autonomic Nervous System (internal environment) o Controls involuntary functions eg respiration, circulation and digestion, stress responses o Many psychoactive drugs affect the brain and autonomic nervous system o Two subdivisions: a) Sympathetic: activation or arousal function, mobilizes body (acetylcholine) b) Parasympathetic: slows down bodily processes, reduce arousal (norepinephrine) E.g. Fight-or-flight response c) Under stress, system will: Speed up heart rate, Dilates pupils, Slows down digestive system (more blood to muscles); Increase respiration rate (more oxygen); Contract vessels d) After stress, system will: Contract pupils, constricts bronchi (lungs), slows heartbeat, stimulates activity in stomach, dilates vessels o Together they maintain Homeostasis: = Humans must maintain their internal environment within certain limits (Temperature, Acidity, Water content, Sodium content, Glucose concentrations, Other physical and chemical factors) 2. CENTRAL NERVOUS SYSTEM  Consists of the brain and the spinal cord  Functions: Integration of information, Learning and memory, Coordination of activity The Brain: Major structures  Cerebral cortex – outmost layer, process sensory info, control muscles, association area, reasoning and language, when awake cerebral cortex is active, less active when sleeping or under influence of sedating drugs  Basal ganglia – maintenance of proper muscle tone (keep legs straight when you are relaxing)  Hypothalamus – near base on brain, above pituitary gland, involved with feeding, drinking, temperature regulation and sexual behaviour; involved with hormonal output  Limbic system – emotion, memory, physical activity – has amygdala, nucleus accumbens and hippocampus – also involved with sexual/eating/natural rewards behaviour  Midbrain, pons, and medulla – part of brain stem; sensory and motor reflexes, control complex movements  Brain stem – connect brain with spinal cord, vomiting centre, regulate breathing Components of Nervous System 1) Glial cells (10x) o Provide firmness and structure to the brain o Get nutrients into the system, Eliminate waste, Form myelin o Communicate with other glia & neurons o Create blood brain barrier that protects brain from toxic chemicals circulating in the blood  It is semipermeable (allowing some but not all chemicals to pass)  for drugs to be psychoactive, its molecules must be small and lipophilic to cross barrier (eg heroine more lipophilic, stronger effects than morphine) 2) Nerve cells – analyzing and transmitting information, over 100 billion in system a. cell body - contains biochemical structures needed to keep the neuron alive and its nucleus carries the genetic information that determines how the cell develops and functions. b. dendrites – tree like features extending form cell body, contain receptors that reiceve and collect messages form neighboring neurons and send to cell body c. axon - conducts electrical signals from cell body to presynaptic terminals (action potential) d. presynaptic terminals – end of axon, chemical messengers (neurotransmitters) are stored in vesicles Neurotransmission  Essential component for communication between neurons is the action potential  Action potential = electrical signal transmitted along axon when a neuron fires, through the release of neurotransmitters (chemical messengers) 1. Resting potential:  Uneven distribution+of ions between -nside and outside of cell o Outside: Na (Sodium) and Cl (Chloride) o Inside: K+ (potassium) and A- (or anions, protein molecules)  MORE  Inside of cell is more negative  Creates negative resting potential (-70mV)  Neuron is in a state of polarization (when membrane potential is more negative) o Hyperpolarization (when membrane potential is below resting potential) 2. Action potential (Nerve Impulse)  Na+ channels open, and Na+ flood into axon  Inside is more positive, cell is depolarized, shift in electrical charge from -70mV to +40mV  To restore resting potential, the cell closes its Na+ and K+ channels on membrane open, K+ flows out of cell (Inside of cell restores negative state, cell is repolarized)  Impulse (Na+) flows down axon to axon terminals and escaped K+ ions are recovered. Chemical Pathways  These neurotransmitters are believed to be mostly associated with psychoactive drugs. 1. Dopamine  Found in basal ganglia and other regions  Nigrostriatal dopamine pathway o Related to muscle rigidity, eg Parkinson’s disease (dopamine deficiency)  Mesolimbic dopamine pathway o Related to psychotic behaviour, eg schizophrenia, overactivation of dopamine o Possible component of the ―reward‖ properties of drugs, leading to abuse and drug dependence 2. Acetylcholine  Pathways w/ acetylcholine found in the cerebral cortex & basal ganglia  Involved in Alzheimer’s disease, learning, memory storage, acetylcholine deficiency  Alcohol extract of Rhodiola Rosea has been associated with inhibition of acetylcholine esterase and memory enhancement  Acetylcholine esterase breaks down acetylcholine to choline and acetic acid thus inactivating it.  Alzheimer’s disease (undersupply), paralysis (absence), violent muscle contrations (oversupply) 3. Norepinephrine  Regulates level of arousal and attentiveness, induce wakefulness  May play a role in initiation of food intake (appetite)  Depression (undersupply), stress/panic (overactivity) 4. Serotonin  Serotonin containing pathways arise in the brain stem raphe nuclei  May have a role in impulsivity, aggression, depression, control of food, and alcohol intake  Hallucinogenic drugs such as LSD influence serotonin pathways  The diet drug Sibutramine causes weight loss by blocking the reuptake of serotonin and norepinephrine (deficient)  Depression, sleeping/eating disorder (undersupply), OCD (overactivity) 5. GABA (Gamma-amino butyric acid)  Found in most regions of the brain  Inhibitory neurotransmitter  Many sedative drugs act by inhibiting GABA , eg Etomidate is a short acting anesthetic and sedative  Strychnine is an example of a GABA blocker  Binding of GABA to its receptors opens a chloride channel, hyperpolarizing the membrane. 6. Glutamate  Found in most regions of the brain  Excitatory neurotransmitter  Connection between glutamate receptors in brain and euphoric effects of cocaine 7. Endorphin  Opioid-like chemical occurring naturally in the brain; also referred to as endogenous morphine  Plays a role in pain relief, other functions  Pain relief from acupuncture related to endorphin  Insentivity to pain (oversupply), pain hypersensitivity (undersupply) Neurotransmitter Type of effect CNS changes Drugs dopamine inhibitory- Euphoria / agitation / paranoia amphetamines, excitatory cocaine acetylcholine excitatory- mild euphoria / excitation tobacco, inhibitory insomnia nicotine serotonin excitatory- Sleep / relaxation / sedation LSD inhibitory GABA inhibitory Sedation / relaxation / drowsinessalcohol, depression Valium-type barbiturates endorphins inhibitory mild euphoria / block pain / slow opioid respiration Drugs and the Brain Life Cycle of a Neurotransmitter 1. Precursors that make neurotransmitters are found circulating in the blood supply 2. Uptake: Selected precursors are taken up by cells, a process requiring energy 3. Synthesis: Precursors are changed (synthesized) into neurotransmitters through the action of enzymes 4. Storage: Neurotransmitters are stored in small vesicles 5. When the action potential arrives, neurotransmitters are released into the synapse (space between neurons) 6. Released neurotransmitters bind with receptors on the membrane of the next neuron 7. Neurotransmitters may have excitatory or inhibitory effects 8. Once a signal has been sent, neurotransmitters are removed from the synapse; may return or be metabolized Examples of Drug Actions  Drugs can directly affect the receptors  It can act as a agonist by mimicking action of neurotransmitter and directly activate the receptor o Interfere with reuptake; eg cocaine blocks reuptake of dopamine o eg Morphine/Endorphin; Cocaine/Dopamine; Nicotine/Acetylcholine; LSD/Serotonin  Or act as an antagonist by occupying the receptor and preventing the neurotransmitter from activating it o eg: Naloxone/Endorphin; Atropine/Acetylcholine; Chlorpromazine/Serotonin Chemical theories of Behavior  No single biochemical theory of drug dependence has achieved sufficient experimental support  Monoamine theory of mood—too little activity in monoamine systems can cause depression, too much can cause mania Brain Imaging techniques  Positron-emission tomography (PET) scan – brain activity o A radioactively labelled chemical (usually glucose) is injected into bloodstream and a computerized scanning device maps out the relative amounts of chemical in various regions of brain o Labelled drugs that bind to dopamine, serotonin or opiate receptors also used to see where binding in brain occurs o Can tell the researcher which part of brain is activated when patient perform certain activities.  Magnetic Resonance Imaging (MRI) – brain structure o The energy released by molecules under a strong magnetic field is examined. o Superior to X-rays in terms of information. o Using computational methods, one can study changes in metabolic activity in regions of the brain. CHAPTER 5–ActionsofDrugs  Source of Drugs o Most drugs come from plants or are chemically derived from plants o If toxic, would be less likely to be consumed by animals and not reproduce, thus eliminate any bad plants through a selection process  Names of drugs o Chemical name: Complete chemical description of the molecule  Example: N'-[2-[[5-(dimethylaminomethyl)-2-furyl] o Generic name: name that specifies a particular chemical but not a particular brand  Example: ranitidine, Diazepam o Brand name: Specific drug or formulation trademarked by manufacturer; can be patented for 20 years  Example: Zantac®, Valium  When newly produced, can be patented for 20 years, so no direct competition  After 20 years, other companies can submit equivalent drugs if can demonstrate similar effects  Cocaine is the preferred injectable drug among Canadian street youth. Categories of Drugs  Stimulants =
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