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Lecture 4

Lecture 4 - Psychopharacology

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Ayesha Khan

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PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 Psychopharmacology Table 4.3; page 122 - Select three drugs out of this table, and make sure you know those three in great deal - Ie. caffine, nicotine, and alcohol  know content in great detail (for short answer or essay portion of the exam) Intro to the lecture - Psychoactive drugs - drug that has the capability to influence a neuron o Some kind of influence on the CNS (doesn’t have to be directly in the CNS Neurotransmitters, Neuromodulators, Neurohormones - Difference has to do with distance o Neurotransmitter is released from neuron A, diffuses from the synapse, and goes to neuron B (close in proximity) o Neuromodulators have he ability to go some distance away (2, or 3 synapses away) and have an impact some difference away o Neurohormones are able to go the furthest. Can be released in the brain and can travel. Because these hormones capitalize movement travelling in the blood.  Bind to carrier protein take this neurohormone some distance away, EXAMPLE: reproductive system and having an impact on the ovaries or testes - Identifying Neurotransmitters o Must be synthesized within the neuron o In response to an action potential, the substance is released in sufficient quantities to produce an effect in the postsynaptic cell o We should be able to duplicate the action of a suspected neurotransmitter experimentally on a postsynaptic cell o Some mechanism exists that ends the interaction between the neurotransmitter and the postsynaptic cell Major Categories of Neurotransmitters, Neuromodulators, and Neurohormones - Classification system is based on what the chemical looks like and made of o Chemicals that have similar molecular characterizes groups of specific neurotransmitters o Size is important, and what is the chemical made up of? - If we have commonalities in terms of size, or building blocks of what the neurotransmitters made up, they get clumped together - Small-mole neurotransmitter o Acetylcholine o Monoamines  Catecholamine  Indolamines PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 o Amino acid neurotransmitter  Flutamate  Gaba o ATP and its byproducts - Neuropeptides – know the basic function o Endorphine - associated with pain reduction o Substance P - important in inflammation responses that occur as a consequence to a damage/pain in the system o CCK - gut/gastro intestinal system  digestion of fat and protein o Insulin - primarily in medical science as a hormone  glucose metabolism o Vasopressin - regulation of water, salts in the blood o Oxytocin – the “boding hormone”, released at the time of birth, or when animals experience a pair bond - Gaseous Neurotransmitters – simply diffuse across the phospholipid bilayer o Nitric oxide – maintaining communication within neurons o Carbon monoxide – important in neural activity PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 Features of Small-Molecule Transmitters & Neuropeptides Small-Molecule Transmitters - Acetylcholine (Cholinergic System) - Catechomamines - Indolamines - Glutamate - GABA The Distribution of Cholinergic Systems in the Brain - Cholinergic nuclei o Located in the pons and midbrain, and basal forebrain and extend all over the brain (forebrain) o Releases acetylcholine Synthesis of Ach by choline acetyltransferase - Formed by two procurers: - Choline – comes from the fat from our diet, and also produced by the liver PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 - Acetyl CoA is generation of metabolism (break down) of fats and sugars that comes from our diet - Choline acetyltransferase* is an enzyme involved - This occurs in the axon terminal (next picture) A Cholinergic Synapse - At the top, we have these building blocks that produce acetylcholine - In the axon terminal, there are lots of enzymes that break down neurotransmitters - As soon as acetylcholine is produced, it needs to be packaged in vesicles - Receptors are protein structures (1)Choline transporter – transports acetylcholine from the axon terminal to the vesicle itself. (Involved marginally) (2) VAChT (Vesicular acetylcholine transporter) – the main receptor involved in transporting - Vesamicol is a drug used, that decreases the amount of acetylcholine that is packaged in a vesicle and released as a consequence - Reuptake of choline and acetate (occur when acetylcholine is broken down in the synapse)  the by products are taken back up - HC-3 impacts this  decreases amount of choline and acetate that is being uptake - Nicotinic and muscarinic receptor  sitting on the postsynaptic neuron that preferentially bind to acetylcholine - AChE is very responsible for the break down PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 Black Widow Spider (Larodectus mactans) - Main function of acetylcholine: o Involved in muscular movement o Health and integrity of movement involved with msucels - There are chemicals in the environment that naturally impact the release of acetylcholine - Can be dramatically effected - There is a toxin found in the venim of the spider, results in a massive release of acetylcholine that a neuron would normally release in a synapse - In a healthy person, the consequence of having too much acetylcholine would be: o Sweating, vomiting, nausesia, tremors (because of muscular movement that are occurring the region) o Not fatal in young healthy adults - In people who are young, or old o Serious consequences can occur o Too much sweating o Because of the tremors, there can be a damage occurring in the lungs Botulinum Toxin: Clostridium botulinum - Botulism - caused when canned food is not properly reserved - Is an example of a bacteria that starts to build up - If it is introduced to a can, it is because the activity of the bacteria can start to change the shape of the can itself - Build up of bacteria occurs because food wasn’t preserved properly, and gains entry into the system - And binds to these vesicles that prevent the release of acetylcholine (decrease in the amount release) - If very little acetylcholine, muscle paralysis can occur o Can be minor o If it travels to the gut, then it can have an effect in the gastro system o Decrease the amount of oxygen if it goes to the lungs o (insert picture here) Botulinum Toxin - Botox is introducing a healthy amount of bacteria in the system for cosmetic purposes - Results in a muscular paralysis - There is chronic contraction of those facial muscles - When injected (locally), it essentially the release of acetylcholine o Muscle paralysis o Or chorionic muscle contraction Breakdown of Ach by Acetylcholinesterase - Acetylcholinerase found in the synapse - Here you have the building block that go back into the neuron itself PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 Peripheral - in flight-or-flight o having an impact in the release of en Alzheimer’s Disease: Behavioural Systems - Minor forgetfulness - Progression to major memory dysfunction - Challenge in planning or solving problems - Difficulty completing familiar tasks at home or at work - Confusion about time or place - Trouble with visual images or spatial relations to name a few….. Alzheimer’s Disease: Cholinergic System - Autopsy: - Loss of cholinergic neurons o Cholinergic tells us that cell body (pons in the midbrain, basal forebrain) start to decrease in number - Also, plaque between neurons - Predictable pattern, beginning in areas important in learning and memory and then spreading to other regions. Alzheimer’s Treatment: Choline? - If you have neurons that are dying, decreasing in number  it means acetylcholine is also decreasing - Why not give a pill that has all these things? - Challenger: Peripheral metabolism o You have lots of enzymes that are sitting in the stomach, gastro intestinal system o If you give the person extra choline and acetyl CoA, there is break down of these products quickly - The focus is on the enzyme that breaks down acetylcholine Alzheimer’s Treatment - Cholinesterase Inhibitors o Donepezil (Aricept) o Rivastigmine (Exelon) o Galantamine (Razadyne) PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 - Memantine o Regulates the activity of glutamate which in turn regulates the activity of acetylcholine o Blocks activity of NMDA receptors Acetylcholine receptor Subtypes - Two major families o Nicotinic receptors – named after to not only binding to acetylcholine, but also being able to bind to nicotine (found in tabacco) o Muscarinic receptors –named after to not only binding to acetylcholine, but also has the ability to bind to a chemical found in agaric muschroom Acetylcholine Receptor Subtypes: Nicotinic - Concentrated on muscle cells at neuromuscular junctions o Neuron synapses - Sympathetic and parasympathetic system o ACh binds to nicotinic receptor o It is ionictropic, so Channel opens rapidly + 2+ o Na and Ca enter the neuron/muscle o Depolarization of cell membrane o  firing o OR muscle contraction Structure of the Nicotinic Ach Receptor PSY290H5S – Introduction to Physiological Psychology Lecture 4 – July 22, 2013 Acetylcholine Receptor Subtypes: Muscarinic - Metabotropic o Five types: M , 1 , 2 , 3 , 4 5 o Second-messenger systems - Stimulation of K channel opening o Hyperpolarization o  cell firing Genetic Deletion of the M5 Muscarinic Receptor - Study showed researchers the impact of acetylcholine associated with an award - There is a award associated in using drugs - M5+/+  genes that are coding for this protein, are functioning appropriating - M5-/-  in these animals, the genes that are coding for this rece
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