Opioids: Pharmacology Lecture Notes PDF

Lecture 9 Pharmacology 2: Opioids PSC 101- Bio Psych February 6th 2024 Lecture 9 Learning Objectives 9.1- Describe how opioid drugs use endogenous opioid receptors to influence pain perception. Be sure to mention the clinical application of opioids. 9.2- Predict how a synapse with...

Lecture 9 Pharmacology 2: Opioids PSC 101- Bio Psych February 6th 2024 Lecture 9 Learning Objectives 9.1- Describe how opioid drugs use endogenous opioid receptors to influence pain perception. Be sure to mention the clinical application of opioids. 9.2- Predict how a synapse with opioid receptors will change due to exposure to high and/or chronic dose(s) of opioids. Explain how these changes will influence behavior. 9.3- Describe how the reward pathway regulates reward seeking behaviors and identify the neurotransmitter receptors used to modulate these behaviors. Explain how opioid tolerance will influence synaptic communication in the pathway and how it will change behavior. 9.4- Explain how an overdose of opioids may be fatal and how naloxone can prevent overdose fatalities. Lecture 9 Learning Objectives 9.1- Describe how opioid drugs use endogenous opioid receptors to influence pain perception. Be sure to mention the clinical application of opioids. 9.2- Predict how a synapse with opioid receptors will change due to exposure to high and/or chronic dose(s) of opioids. Explain how these changes will influence behavior. 9.3- Describe how the reward pathway regulates reward seeking behaviors and identify the neurotransmitter receptors used to modulate these behaviors. Explain how opioid tolerance will influence synaptic communication in the pathway and how it will change behavior. 9.4- Explain how an overdose of opioids may be fatal and how naloxone can prevent overdose fatalities. 9.1- Opioids and Pain What are opioids and what do they do to the body? Take 1-minute to think about your answer Pair up with a person next to you and talk about your answer (if you are comfortable) Share your answers with me! (if you are comfortable) 9.1- Opioids and Pain What are opioids and what do they do to the body? Possible Answers: pain supression Feel ingof enjoyment or joy Hyperactivity 9.1- Opioids and Pain Opioid Receptors The body has multiple opioid receptors Receptors named after the substance that was discovered to activate them Common for old school naming of receptors 9.1- Opioids and Pain Opioid Receptors These receptors regulate a wide range of processes: Pain perception Reward Seeking Behaviors Hedonic Pleasure Respiration More Activated by NTs called endogenous opioids Aka endorphins 9.1- Opioids and Pain Opioids/Opiates Opiates are natural occurring substances produced by the opium poppy Active agent of a broad range of clinically used medications and illegal recreational drugs 9.1- Opioids and Pain Opioids/Opiates Opioids are the general term for the naturally produced opiates from opium poppies and synthetic substances with same mechanism of action 9.1- Opioids and Pain Opioids/Opiates Morphine Heroin Fentanyl Codeine Oxycodone Etc. 9.1- Opioids and Pain Opioids/Opiates Opioids are agonists for opioid receptors When opioids bind to the receptors, the receptor activates 9.1- Opioids and Pain Pain Subdivision of sensory neurons in the PNS encodes for pain Axons carry pain information from the body to the CNS Useful tool for: Avoiding harmful stimuli Being aware of possible damage to the body Learning 9.1- Opioids and Pain Endogenous Opioid Pain Suppression Suppressing pain perception is important for certain survival situations Ex. Running from danger Some neurons with opioid receptors inhibit the signaling of pain receptors 9.1- Opioids and Pain Endogenous Opioid Pain Suppression When endogenous opioids activate these receptors, pain sensory neurons are inhibited Temporarily reducing or eliminating pain perception 9.1- Opioids and Pain Opioids and Pain Primary clinical use of opioid drugs is for pain management Takes advantage of the pain suppression signaling of endogenous opioids 9.1- Opioids and Pain Opioids and Pain Opioid drugs bind to opioid receptors Effectively and efficiently inhibiting the pain sensory neurons Blocking the pain from reaching the brain Will never perceive the pain 9.1- Opioids and Pain 2-Minute Neuroscience: Opioids https://youtu.be/NPlNCqBHPnE?si=WF2ert6FxrRaV6i4 Time: 0:00 – 1:30 9.1- Opioids and Pain Opioids- Pain Management Unbelievably important tool to help people mitigate pain due to: Injury Disease Medical procedure recovery Etc. 9.1- Opioids and Pain Double-Edged Sword Opioid drugs do not act on only pain receptors Opioid drugs will activate all the opioid receptors across the body Leading to other side effects Self-Assessment Questions Get your iClicker app or web portals ready! Lecture 9 Learning Objectives 9.1- Describe how opioid drugs use endogenous opioid receptors to influence pain perception. Be sure to mention the clinical application of opioids. 9.2- Predict how a synapse with opioid receptors will change due to exposure to high and/or chronic dose(s) of opioids. Explain how these changes will influence behavior. 9.3- Describe how the reward pathway regulates reward seeking behaviors and identify the neurotransmitter receptors used to modulate these behaviors. Explain how opioid tolerance will influence synaptic communication in the pathway and how it will change behavior. 9.4- Explain how an overdose of opioids may be fatal and how naloxone can prevent overdose fatalities. 9.2- Tolerance Endogenous Opioids in the Brain Opioid receptors in the brain are important for modulating multiple cognitive processes: Hedonic Pleasure Reward-Seeking Behavior Play Behaviors More! Endogenous opioids are released in small quantities True for most NT signaling A little bit goes a long way 9.2- Tolerance Opioid Drugs in the Brain Opioid drugs will interact with all opioid receptors in the brain and body Influencing psychological and physiological processes Concentration of opioid drugs is significantly larger than naturally released endogenous opioids 9.2- Tolerance Acute Effect of Opioids Opioid drugs will oversaturate synapses Greatly activating opioid receptors Changing behavior and perception opioids Pain Euphoria Reward seeking behaviors 9.2- Tolerance are cleft Endo Opioids NT Base line posts Opioid receptors 9.2- Tolerance 4 activate of release some Endo opioid Opioid receptors 9.2- Tolerance 9.2- Tolerance opioid sig great drug Ligand 9.2- Tolerance ate the cell 1 I 9.2- Tolerance Acute Effect of Opioids Short-term behavioral and perceptual changes are typically the desired outcome for opioid users Clinical Pain suppression Recreational Euphoria 9.2- Tolerance Homeostasis counteract This extreme activation of opioid receptors is a deviation Increased from the normal Opioidrespo Body wants to maintain at homeostasis Seesaw Will modify neural structures to adapt to abnormal stimuli 9.2- Tolerance arge dose of opioid drug 9.2- Tolerance Return to Baseline overactivated 9.2- Tolerance Fewer receptors remove opioid receptors 9.2- Tolerance Long-Term Effects of Opioids The synapse will want to return to normal activation levels Neurons will detect the over activation of opioid receptors Opioid receptors are removed from the membrane Will have weaker response to the same amount of ligand 9.2- Tolerance Following these synaptic changes, will the same dose of opioids have the same effect? Take 1-minute to think about your answer Pair up with a person next to you and talk about your answer (if you are comfortable) Share your answers with me! (if you are comfortable) 9.2- Tolerance Following these synaptic changes, will the same dose of opioids have the same effect? Possible Answers: 9.2- Tolerance Tolerance The drug dose must be increased to obtain the same effect Higher dose will cause an over activation of the synapse again Resulting in more synaptic changes 9.2- Tolerance fewer receptors 9.2- Tolerance dose 9.2- Tolerance 9.2- Tolerance 9.2- Tolerance 9.2- Tolerance 9.2- Tolerance 9.2- Tolerance Tolerance Decrease of receptors will influence the response to both: Opioid Drugs Endogenous Opioids Opioid receptor mediates behaviors that will be suppressed following tolerance Increased pain sensitivity Decreased hedonic pleasure Increased reward seeking behaviors 9.2- Tolerance Recovery It is unclear if the synapses return to how they were before tolerance Possible recovery could take years to return to normal endogenous opioids Major drive for relapsing for people with substance use disorder Self-Assessment Questions Get your iClicker app or web portals ready! Lecture 9 Learning Objectives 9.1- Describe how opioid drugs use endogenous opioid receptors to influence pain perception. Be sure to mention the clinical application of opioids. 9.2- Predict how a synapse with opioid receptors will change due to exposure to high and/or chronic dose(s) of opioids. Explain how these changes will influence behavior. 9.3- Describe how the reward pathway regulates reward seeking behaviors and identify the neurotransmitter receptors used to modulate these behaviors. Explain how opioid tolerance will influence synaptic communication in the pathway and how it will change behavior. 9.4- Explain how an overdose of opioids may be fatal and how naloxone can prevent overdose fatalities. 9.3- Reward Pathway Opioids and the Reward Pathway Neural adaptations due to opioid drugs will change synaptic communication in the brain’s reward pathway Changes in the reward pathway will significantly influence behavior 9.3- Reward Pathway Reward Pathway Series of brain areas important for the regulation of reward seeking behaviors DA produced in ventral tegmental area (VTA) One of the multiple DA producing regions in the midbrain 9.3- Reward Pathway Reward Pathway Axons from the VTA project to the nucellus accumbens (NA) and the cortex Pathway most active during behaviors associated with motivation and reward seeking behaviors 9.3- Reward Pathway Dopamine Misconceptions Pop culture often refers to dopamine (DA) as the “happiness” molecule Drugs that result in experiencing euphoria activate DA neurons Assuming that DA is the signal responsible for experiencing euphoria 9.3- Reward Pathway Dopamine Misconceptions Deeper inspection has shown that DA is not responsible for feeling “happy” Might be an aspect, but not the major signaling molecule 9.3- Reward Pathway DA Reward Experiment Recording from the DA producing cells of the VTA in mice Electrode in Fire APs when DA is released MY VTA Examine activity when: Unexpectantly receive a reward Cue for upcoming reward and then receive it Cue for upcoming reward and then don’t receive it 9.3- Reward Pathway conditioned increase no stimuli Large activit of VTA AP more LessA AT 7 reward reward Neural activity 9.3- Reward Pathway DA Release DA Reward 9.3- Reward Pathway PArelease 9.3- Reward Pathway 9.3- Reward Pathway DA Reward Experiment- Results VTA cells are active when: Receiving an unexpected reward Cue associated with reward is presented VTA cells are not active when receiving an expected reward 9.3- Reward Pathway DA Reward Experiment- Results DA signaling is not crucial for “enjoying” a stimuli DA is crucial for “wanting” and reward seeking behavior Encodes for: Learning about rewarding stimuli Responding to information associated with a reward 9.3- Reward Pathway “Liking” Signaling DA does not exclusively mediate “liking” or hedonic pleasure Most likely a complex interaction amongst: Opioid receptors Endocannabinoid receptors DA receptors 9.3- Reward Pathway Reward Pathway Physiology The NA has DA and opioid receptors to mediate reward seeking behaviors Release of endogenous opioids will enhance the activity of DA axons 9.3- Reward Pathway Axon from the VTA DA Interneuron Inhibne DA Neuron Dendrite in the VTA the from NA postsynapticcell 9.3- Reward Pathway opioid Inhibited Non Interneuron Rewardind Less stimuli Inhibited Endo opioids Intlib the DA neuron less 0 Release Greater moreDA activation 9.3- Reward Pathway Reward Pathway Physiology Opioid receptors inhibit an interneuron, reducing its inhibition of the DA axon DA release is increased Activation of opioid receptors will enhance DA signaling, encoding rewarding stimuli 9.3- Reward Pathway Opioids in Reward Pathway Opioids will oversaturate opioid receptors on interneurons Greatly inhibiting interneurons DA synaptic signaling is greatly enhanced 9.3- Reward Pathway Baseline moderate Inhibition 9.3- Reward Pathway overactivation Highly active step opioid Inhibition drug Highly active 9.3- Reward Pathway Opioids in Reward Pathway NA will encode opioid stimuli as an extremely rewarding experience DA release will be significantly more salient than non-opioid stimuli Increasing motivation to have repeated exposure to the opioid stimuli 9.3- Reward Pathway Opioids in Reward Pathway Increasing the motivation to have repeated exposure to the opioid stimuli Behaviors will prioritize experiencing more opioid stimuli over non-opioid stimuli Ex. food, intercourse, social interactions, etc. 9.3- Reward Pathway Tolerance in the Reward Pathway The NA will experience opioid tolerance with high and/or chronic doses of opioids Fewer opioid receptors on the interneurons Less sensitive to opioid drugs and endogenous opioids Increased inhibition on DA cell 9.3- Reward Pathway Tolerance in the Reward Pathway Non-opioid stimuli will be even less “rewarding” Same number of endogenous opioids activating significantly fewer opioid receptors Opioid stimuli will be more “rewarding” if opioid doses are increased Increased number of opioids to activate the decreased number of opioid receptors 9.3- Reward Pathway Reward Pathway Changes Brain structures responsible for reward seeking are re-wired Behaviors change to prioritize experiencing opioid stimuli over non-opioid stimuli As tolerance increases, drug seeking behaviors increases Positive feedback loop 9.3- Reward Pathway Substance Use Disorder Changes of neuroanatomy and behaviors result in physical and psychological dependance on opioid drugs Resulting in substance use disorder 9.3- Reward Pathway Substance Use Disorder Aka, addition Being recontextualized as a disease model, rather than personal choice Acknowledging the physiological changes in the brain that influence behaviors 9.3- Reward Pathway Substance Use Disorder Neurological changes can occur due to: Few large dose exposures Chronic exposures Motivation for: Closely monitored clinical pain management Illegalization of recreational use 9.3- Reward Pathway National Geographic: What is What Happens to Your Brain on Opioids https://youtu.be/NDVV_M__CSI?si=bhzp9a8vYcy1olDo Time: 0:00 – 4:02 Self-Assessment Questions Get your iClicker app or web portals ready! Lecture 9 Learning Objectives 9.1- Describe how opioid drugs use endogenous opioid receptors to influence pain perception. Be sure to mention the clinical application of opioids. 9.2- Predict how a synapse with opioid receptors will change due to exposure to high and/or chronic dose(s) of opioids. Explain how these changes will influence behavior. 9.3- Describe how the reward pathway regulates reward seeking behaviors and identify the neurotransmitter receptors used to modulate these behaviors. Explain how opioid tolerance will influence synaptic communication in the pathway and how it will change behavior. 9.4- Explain how an overdose of opioids may be fatal and how naloxone can prevent overdose fatalities. 9.4- Naloxone Opioids’ Effects on Respiration Opioid receptors are also important for regulating respiration (aka breathing) Activation of opioid receptors will suppress breathing Important for parasympathetic responses 9.4- Naloxone Opioid ODs Deaths due to opioid overdose (OD) are typically due to asphyxiation following over suppression of the respiratory system Increased doses following tolerance increases likelihood of ODing 9.4- Naloxone Naloxone Commercial name: Narcan Opioid receptor antagonist Counteracts immediate effects of opioids 9.4- Naloxone Naloxone Can be administered to revert respiratory arrest due to opioid OD Will block the opioid receptors across the whole body 9.4- Naloxone Why do we have an opioid epidemic if naloxone counteracts the effects of opioids? Take 1-minute to think about your answer Pair up with a person next to you and talk about your answer (if you are comfortable) Share your answers with me! (if you are comfortable) 9.4- Naloxone Why do we have an opioid epidemic if naloxone counteracts the effects of opioids? Possible Answers: 9.4- Naloxone Naloxone Naloxone will block the effect of opioids Will not be able to undo the neurological changes that influence behaviors 9.4- Naloxone National Library of Medicine- How Naloxone Saves Lives in Opioid Overdose https://youtu.be/VitFvNvRIIY?si=gAstj-nXScIe3krh Time: 0:00 – 4:40 9- Wrap Up Opioid Research Major field of research to better understand: Mechanism and risk factors for substance use disorder Development of non-addictive opioids for clinical use Recovery from opioids mediated synaptic changes To learn more about opioids other addictive drugs, enroll in: NPB 068 or 168 Any questions? Slides were made by Brett M. Bormann, UC Davis Neuroscience Graduate Group