Chapter 3 Drugs And The Nervous System


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  • What about religious belief, does that also stimulate the Mesolimbic Dopaminergic pathway? I have always wondered if that is why so many drug addicts turn to religion-it replaces the drugs?
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Chapter 3 Drugs And The Nervous System

  1. 1. Drugs and the Nervous System Chapter 3
  2. 2. Introduction <ul><li>Why is it important to study the nervous system when learning about drug effects on the body ? </li></ul><ul><li>Every feeling or emotion you have – in fact, all psychological experience – is based on brain activity </li></ul><ul><li>The brain is the basis of conscious experience and it is the key organ of the nervous system </li></ul><ul><li>All psychoactive drugs produce their effects by acting in some way on nervous system tissue </li></ul><ul><li>Most of these actions occur at the level of the brain </li></ul>
  3. 3. The Neuron <ul><li>Neuron – The individual nerve cell is the basic building block of the nervous system. Similar to other cells but they have the unique feature of being able to communicate with each other </li></ul><ul><li>Structural properties of neurons include: </li></ul><ul><li>Nucleus – Contains genetic material and other processes that control metabolic activities of the cell </li></ul><ul><li>Dendrite – Spiny branchlike structures that extend from the cell body of a neuron; typically contain numerous receptor sites and are thus important in neural transmission </li></ul>
  4. 4. <ul><li>Axon – A long cylindrical extension of the cell body of the neuron; conducts an electrical charge from the cell body to the axon terminals. Axons vary in length and are sometimes thousands of times longer than the diameter of the cell body </li></ul><ul><li>Myelin – A fatty, white substance that covers the axons of some neurons and provides insulation similar to insulation for a wire </li></ul><ul><li>Action Potential – The electrical impulse or signal transmitted along the axon that occurs when a neuron fires. It is produced by the flow of charged particles called ions in and out of the axon </li></ul>
  5. 5. Neural Transmission <ul><li>Neural transmission occurs without direct contact between the neurons. It may be thought of as an electrochemical event – electrical along the axon and chemical at the synapse. It involves the following: </li></ul><ul><li>Axon Terminal (or terminal button ) – Enlarged buttonlike structures at the ends of axon branches </li></ul><ul><li>Synapse – The junction between neurons </li></ul><ul><li>Neurotransmitters – Chemical substances stored in the axon terminals that are released into the synapse when the neuron fires. Neurotransmitters then influence activity in postsynaptic neurons </li></ul>
  6. 6. <ul><li>A lock-key analogy is useful for depicting the neural transmission process </li></ul><ul><li>Receptor Sites – Specialized structures located on dendrites and cell bodies for neurons that are activated by neurotransmitters. They can be viewed as locks that must be opened or “unlocked” by the neurotransmitter “keys” before the neuron fires </li></ul><ul><li>The key must fit the lock in order to trigger the firing </li></ul><ul><li>When a neurotransmitter molecule binds to a receptor, changes occur in the neuron that make it more or less likely to fire. Mechanisms for these changes are: </li></ul>
  7. 7. <ul><li>Ionotropic Receptors – Receptors coupled to the ion channels that regulate the number of charged molecules inside and outside the neuron. When a transmitter binds to this receptor, the channel opens and allows charged particles to enter or leave the cell </li></ul><ul><li>Excitatory Transmission – Occurs when there are more positively charged ions inside the cell generating an action potential </li></ul><ul><li>Inhibitory Transmission – When channels are opened that result in fewer positively charged ions inside the neuron making it less likely to fire </li></ul><ul><li>Ionotropic receptors are termed “fast” receptors because the entire process is completed in just a few milliseconds </li></ul>
  8. 8. <ul><li>Metabotropic Receptors – Receptors that are said to be “slow” because they produce changes that are slightly delayed (by a few hundred milliseconds) and can be long-lasting. </li></ul><ul><li>They are not directly coupled with ion channels but cause the release of specialized molecules called “second messengers” </li></ul><ul><li>They can increase the likelihood of firing (excitatory) or decrease it (inhibitory) </li></ul><ul><li>There are many different types of neurotransmitter keys and many corresponding receptor site locks </li></ul>
  9. 9. Drugs and Neural Transmission <ul><li>Most psychoactive drugs produce their effects by action at the synapse. Drugs effects can be produced by altering the following neurochemical systems: </li></ul><ul><li>Neurotransmitter synthesis – A drug may increase or decrease the synthesis or production of neurotransmitters </li></ul><ul><li>Neurotransmitter transport – A drug may interfere with the transport of neurotransmitter molecules to the axon terminals. If the substance is manufactured in the cell body it must still be transported to the terminal before it is functional </li></ul>
  10. 10. <ul><li>Neurotransmitter storage - A drug may interfere with the storage of neurotransmitters in the vesicles of the axon terminal. For example, the drug reserpine, causes certain vesicles to become leaky and then the transmitters involved are not effectively released into the synapse </li></ul><ul><ul><li>Vesicles – Tiny sacs in axon terminals that store neurotransmitters </li></ul></ul><ul><li>Neurotransmitter release - A drug may cause the axon terminals to release neurotransmitter molecules into the synapse prematurely. Stimulant drugs such as amphetamines are thought to act this way </li></ul>
  11. 11. <ul><li>Neurotransmitter degradation – A drug may influence the breakdown of neurotransmitters by enzymes. It can alter neural transmission by affecting enzyme activity. Some antidepressant drugs alter brain levels of the neurotransmitters norepinephrine, dopamine, and </li></ul><ul><li>serotonin by inhibiting the activity of monoamine oxidase, the enzyme that breaks down these compounds </li></ul><ul><ul><li>Enzyme Breakdown – One process by which neurotransmitters are inactivated. Chemicals called enzymes interact with the transmitter molecule and change its structure so that it no longer is capable of occupying receptor sites </li></ul></ul>
  12. 12. <ul><li>Neurotransmitter reuptake - A drug may block the reuptake of neurotransmitters into the axon terminals. Cocaine exerts some of its action by blocking the reuptake process </li></ul><ul><ul><li>Reuptake – One process by which neurotransmitters are inactivated. Neurotransmitter molecules are taken back up into the axon terminal that released them </li></ul></ul><ul><li>Receptor activation – A drug may activate a receptor site by mimicking a neurotransmitter, similar to a duplicate key that fits into and opens the locks. Morphine and heroin mimic natural neurotransmitters called endorphins </li></ul><ul><li>Receptor blocking – A drug may cause a receptor to become inactive by blocking it </li></ul>
  13. 13. <ul><li>Some drugs act as if they fit into the lock but then jam it and prevent it from firing. Such a drug is called a blocking agent . Any chemical, natural or otherwise, that fits a receptor lock and activates it is said to be an agonist of that receptor. Any compound that occupies a receptor and does not activate it, but prevents other compounds from activating it, is said to be an antagonist . </li></ul><ul><ul><li>Agonist (Enhance) – A substance that occupies a neural receptor and causes some change in the conductance of the neuron </li></ul></ul><ul><ul><li>Antagonist (Inhibit) – A substance that occupies a neural receptor and blocks normal synaptic transmission. Naloxone is an antagonist of the receptors on which opiate drugs such as heroin work </li></ul></ul>
  14. 14. Major Neurotransmitter Systems <ul><li>Acetylcholine – A neurotransmitter found both in the brain and in the parasympathetic branch of the autonomic nervous system that is linked with memory processes. One of the first neurotransmitters to be discovered because found in the neurons outside the brain </li></ul><ul><ul><li>Neuromuscular Junction – Junction or space similar to the synapse, between neuron and muscle fibers where release of acetylcholine by neurons causes muscles to contract. Some muscle disorders are related to problems with this process. </li></ul></ul><ul><ul><li>Myasthenia gravis, a disease characterized by severe muscle weakness and fatigue is caused by a blockage of acetylcholine at the neuromuscular junction. </li></ul></ul>
  15. 15. <ul><ul><li>Botulinum, one of the deadliest toxins known, which also blocks the release of acetylcholine at the neuromuscular junction results in muscle paralysis, and in sufficient doses, death by asphyxiation. </li></ul></ul><ul><ul><li>A carefully prepared form of botulinum toxin is marketed as Botox and used cosmetically to smooth facial wrinkles and lines . </li></ul></ul><ul><li>Evidence suggests Alzheimer’s disease may be related to loss of neural function in some of the brain’s cholinergic pathways, and thus, drugs that reduce it’s symptoms are thought to elevate acetylcholine in the brain </li></ul>
  16. 16. <ul><ul><li>Alzheimer’s Disease – One of the most common forms of senility among the elderly; involves a progressive loss of memory and other cognitive functions </li></ul></ul><ul><ul><li>Note: If the name of a neurotransmitter is to be used as an adjective, take the stem of the name (i.e., choline ) and add the suffix “ ergic ”. Thus neurons that contain acetylcholine are cholinergic neurons and drugs that block acetylcholine, such as atropine, are anticholinergic drugs. Nicotine is an example of a cholinergic drug: it is an agonist at acetylcholine receptors in some parts of the brain </li></ul></ul>
  17. 17. <ul><li>Monoamines – A class of chemicals characterized by a single amine group; includes the neurotransmitters: norepinephrine (noradrenaline), dopamine, and serotonin </li></ul><ul><ul><li>Norepinephrine – A neurotransmitter that is involved in activity of the of the sympathetic branch of the autonomic nervous system. Outside the brain it mediates physical changes that accompany emotional arousal; inside it is important in the regulation of hunger, alertness, and arousal </li></ul></ul><ul><ul><li>Serotonin – A neurotransmitter found throughout the brain that is involved with sleep and mood. </li></ul></ul>
  18. 18. <ul><li>Dopamine – A neurotransmitter in the brain that is involved with coordinated movement and reward. It is hypothesized that dopamine insufficiency may be the basis of Parkinson’s Disease . </li></ul><ul><ul><li>Parkinson’s Disease – A disease that primarily afflicts the elderly and involves a progressive deterioration of motor control. Symptoms include loss of fine motor movements, muscle rigidity, and tremor </li></ul></ul><ul><ul><li>L-Dopa – A chemical precursor of dopamine used in the treatment of Parkinson’s disease </li></ul></ul><ul><ul><li>Blood-brain Barrier – The system that “filters” the blood before it can enter the brain protecting it from toxic chemicals. L-Dopa is able to penetrate this barrier and is converted into dopamine </li></ul></ul>
  19. 19. <ul><li>As the monoamine neurotransmitters are closely linked to mood states and emotional disorders, drugs that influence them have revolutionized modern psychiatry </li></ul><ul><li>It is proposed that clinical depression is associated with disregulation of monoamines, particularly norepinephrine and serotonin </li></ul><ul><li>Theory originated with the finding that certain drugs that depleted monoamines seemed to produce depression and drugs that are useful in treating depression (e.g., Prozac) influence either norepinephrine or serotonin transmission or both. </li></ul><ul><li>Evidence of abnormal monoamine activity in clients who suffer from depression has been reported </li></ul>Depression
  20. 20. Schizophrenia <ul><li>Involves a major loss of contact with reality and is characterized by false beliefs or delusions, hallucinations, social withdrawal, and distortions of emotionality. </li></ul><ul><li>Strong evidence ties these symptoms to high levels of monoamine activity </li></ul><ul><li>Drugs that are effective in treating schizophrenia block monoamine transmission, specifically dopamine receptors </li></ul><ul><li>Stimulant drugs such as cocaine and amphetamines increase monoamine activity in the brain and in high doses often lead to paranoid delusions and a loss of reality contact that strongly resembles some symptoms of schizophrenia </li></ul>
  21. 21. CONTEMPORARY ISSUE BOX 3.1 You Are Never Too Old to Make New Neurons: Adult Neurogenesis and Depression <ul><li>Research now shows that in the hippocampus and some areas of the cerebral cortex, neurogenesis (new brain cell development) may occur throughout adulthood </li></ul><ul><li>A link between neurogenesis and depression is suspected since studies show that various types of stress can suppress production of new neurons and stress is linked to depression </li></ul><ul><li>Elevated serotonin levels increase neurogenesis and antidepressant medication generally elevates serotonin </li></ul><ul><li>Such findings hold promise for more effective treatments of depression </li></ul>
  22. 22. Other Transmitters <ul><li>Endorphins (endogenous morphine) – Neurotransmitters in the brain that modulate pain relief and are mimicked by opiate drugs such as morphine and heroin </li></ul><ul><li>GABA – Short for gamma-aminobutyric acid, the most abundant inhibitory neurotransmitter in the brain. Drugs that act on the GABA system are the depressant drugs such as barbiturates, tranquilizers such as Valium and Librium, and alcohol </li></ul>
  23. 23. <ul><li>Glutamate – Among the most abundant of the excitatory amino acid neurotransmitters. Some hallucinogenic drugs (PCP, Ketamine) act on glutamate receptors in parts of the brain </li></ul><ul><li>Adenosine – Another inhibitory neurotransmitter which is thought to be blocked by caffeine. So caffeine appears to produce its stimulant effects through a sort of disinhibition </li></ul><ul><li>Anandamide – One of the most recently discovered neurotransmitters. This lipid neurotransmitter is mimicked by the active chemical in marijuana </li></ul>
  24. 24. The Nervous System <ul><li>Central Nervous System (CNS) – The brain and the spinal cord </li></ul><ul><li>Peripheral Nervous System (PNS )– All nervous tissue outside (or peripheral to) the CNS. Includes nerves (nerves are simply bundles of axons) that send input from the senses to the brain (sensory nerves), and nerves that send output from the brain to muscles (motor nerves), and the automatic nervous system </li></ul><ul><li>Autonomic Nervous System (ANS) – Part of the PNS that regulates various nonconscious or automatic functions; has two branches: sympathetic and parasympathetic </li></ul>
  25. 25. <ul><li>Sympathetic Branch – Branch of the ANS that is activated during emotional arousal by a release of epinephrine and norepinephrine from the adrenal glands. Responsible for such physiological changes as increased heart and respiratory rate, increased blood pressure, increased sweating ,and pupil dilation as blood flow is directed away from internal organs to the brain and large muscle groups ( “fight of flight” reaction) </li></ul><ul><li>Sympathomimetic – Drugs such as amphetamines, cocaine, and some hallucinogens such as LSD mimic sympathetic arousal by producing the physiological effects of sympathetic activity </li></ul>
  26. 26. <ul><li>Beta-blockers – Drugs that block a type of norepinephrine receptor in the sympathetic system called “beta” receptors that regulate blood pressure. Drugs such as propranolol are widely used in the treatment of hypertension </li></ul><ul><li>Parasympathetic Branch – Branch of the ANS that in general balances the actions of the sympathetic branch by exerting opposite effects such as lowering heart rate and blood pressure and so on. Drugs like nerve gases that act directly on this system can be highly toxic by causing excessive parasympathetic activity such as respiratory or cardiovascular activity. Atropine, an antagonist at acetylcholine receptors, is an antidote to nerve gas </li></ul>
  27. 27. The Brain <ul><li>The brain is the key organ of the nervous system. It is covered with a tough membrane called meninges and floats within the skull in a liquid known as cerebrospinal fluid . It contains billions of neurons with billions of synapses. Major divisions of the brain include: </li></ul><ul><li>Hindbrain – Lower part of the brain located just above the spinal cord, including the medulla, pons, and cerebellum. It </li></ul><ul><ul><li>Medulla Oblongata – Lowest hindbrain structure of the brain; important in the regulation of breathing, heart rate, blood pressure, vomiting, swallowing, and other basic life functions </li></ul></ul>
  28. 28. <ul><ul><li>Normal functioning of the medulla is critical so when toxic chemicals reach high levels in this area, the vomit center is triggered to purge the body, which may be why drinking large quantities of alcohol often cause nausea and vomiting </li></ul></ul><ul><ul><li>Pons – Hindbrain structure important in the control of sleep and wakefulness </li></ul></ul><ul><ul><li>Reticular Activating System – Pathway running through the medulla and pons that regulates alertness and arousal. Drugs that lower arousal and induce sleep (such as barbiturates and tranquilizers) are thought to act in this region of the brain </li></ul></ul>
  29. 29. <ul><ul><li>Cerebellum – Hindbrain structure important in motor control and coordination. Activities are largely unconscious but do involve balance, coordinated movements of all kinds, and speech. Loss of motor control and balance produced by drugs such as alcohol may be due to their action on this area </li></ul></ul><ul><li>Midbrain – Includes the inferior and superior colliculi and the substantia nigra. </li></ul><ul><ul><li>Inferior Colliculi – Form part of the auditory system and thus controls sound localization </li></ul></ul><ul><ul><li>Superior Colliculli –Controls visual localization </li></ul></ul>
  30. 30. <ul><ul><li>The colliculi structures are specifically involved with localization of stimuli and medication of reflexes only. Actual recognition and interpretation of stimuli take place elsewhere in the brain </li></ul></ul><ul><ul><li>Substantia Nigra – Literally “black substance”, this basal ganglia structure is darkly pigmented; produces dopamine. Damage to this area produces Parkinson’s disease after about 80% of the substantia nigra is destroyed. Some toxins including some “designer drugs” (MTPT- highly toxic derivative of the designer heroin MPPP) appear to be capable of killing neurons in this region and triggering the disorder </li></ul></ul>
  31. 31. <ul><li>Forebrain – Largest part of the human brain which includes the most important brain regions from the perspective of interpreting complex human behavior: thalamus, hypothalamus, basal ganglia, cerebral cortex, and limbic system </li></ul><ul><ul><li>Thalamus – A type of relay station that receives incoming sensory stimuli, organizes it, then “relays” it to relevant centers throughout the brain </li></ul></ul><ul><ul><li>Hypothalamus – Critical structure in the motivation of behavior. It regulates eating, drinking, aggression, sexual behavior, and other basic biological drives </li></ul></ul>
  32. 32. <ul><li>The limbic system, the basal ganglia, and cerebral cortex are complex systems controlling aspects of behavior that are most uniquely human such as complex reasoning, memory, logic, speech, and planning </li></ul><ul><li>Limbic System – Includes several structures in the interior of the forebrain such as the amygdala and hippocampus </li></ul><ul><ul><li>Amygdala – Mediates certain types of aggression and other emotional experience </li></ul></ul>
  33. 33. <ul><ul><li>Hippocampus – A structure of the limbic system thought to be important in the formation and storage of memories. Persons with damage to this area may have long-term memories in tact but they cannot form new permanent memories </li></ul></ul><ul><li>Basal Ganglia – Forebrain structures important for motor control; include the caudate nucleus, the putamen, and the globus pallidus </li></ul><ul><li>Cortex – Outermost and largest part of the human brain distinguished from those of most other animals by its size. Involves many of the complex psychological functions characteristically human </li></ul>
  34. 34. <ul><ul><li>Occipital lobe – Visual projection area at the back of the brain </li></ul></ul><ul><ul><li>Temporal lobe – Auditory stimulation and language. Damage to the left lobe results in severe impairment in language abilities (right-handed), right lobe damage results in disregulation of emotions. Relationship between right and left temporal lobe mediation of language and emotions is reversed in some cases (e.g., left-handed individuals). </li></ul></ul><ul><ul><li>Frontal lobe – Initiation of motor movement, emotionality, intelligence, and personality </li></ul></ul><ul><ul><li>Parietal lobe - Tactile stimuli </li></ul></ul>
  35. 35. The Neural Basis of Reward <ul><li>Mesolimbic Dopaminergic Pathway – Pathway that is rewarding when stimulated and thus referred to as the “pleasure center” </li></ul><ul><li>This brain region is significant in understanding the rewarding properties of drugs as it is rich in dopamine, a critical chemical in producing such properties </li></ul><ul><li>Many pleasurable events result in the release of dopamine in this pathway – good tasting food (especially chocolate), sex, and drugs such as cocaine, heroin, and nicotine </li></ul><ul><li>It is oversimplification to say that dopamine release always translates into pleasure since events such as electric shock also release dopamine </li></ul>
  36. 36. Imaging the Human Brain <ul><li>Electroencephalography (EEG ) </li></ul><ul><li>Technique used to measure electrical activity in the brain. Brain waves change in predictable ways and abnormalities in EEG patterns can reveal gross brain damage </li></ul><ul><li>Computerized Axial Tomography (CT or CAT scan ) </li></ul><ul><li>Technique that produces a three-dimensional X-ray image of the brain. Focus can be changed to different depths of the brain to detect internal tumors, enlarged spaces or ventricles, and other internal abnormalities </li></ul>
  37. 37. <ul><li>Positron Emission Transaxial Tomography (PET) Technique used to measure activity/functioning in selected brain regions. The PET and the closely related SPECT (single photon emission computed tomography) scan promise to greatly increase our ability to detect subtle brain damage that drugs may induce </li></ul><ul><li>Magnetic Resonance Imaging (MRI) – Technique that creates a high-resolution, three-dimensional image of the brain that may improve our ability to detect and understand brain dysfunction. A modification of the MRI called functional MRI (fMRI) permits very rapid imaging and enables us to measure oxygen levels in blood vessels of the brain </li></ul>
  38. 38. <ul><li>That’s all </li></ul><ul><li>folks ! </li></ul>