4/23/15 – Lecture 25 – Psychopharmacology and the basics of Drug Addiction- Goal – to understand how drugs affect the nervous system- Psychopharmacology – the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior- Psychoactive Drugs – any substance that alters mood, thought, or behavioro Most psychoactive drugs influence synaptic transmission 7 Main Sites of Drug Addiction- Neurotransmitter Synthesis – in the cell body, axon, or terminal- Neurotransmitter Storage – transports into vesicles- Neurotransmitter Release – how many vesicles fuse per Action Potential- Receptor Interaction- Inactivation- Reuptake- Degradationo An agonist is any drug that increases neurotransmissiono An antagonist is any drug that decreases neurotransmission Both can work on any of the 7 sites of drug action Examples of Agonists and Antagonists – Cholinergic System- Choline-poor diet – antagonist, decreases synthesis- Black Widow spider venom – agonist, increased release- Botulinum toxin – antagonist, inhibits release- Nicotine – agonist, activates receptors- Curare – antagonist, blocks receptors- Physostigmine – agonist, blocks inactivationo FOR TEST – figure out how to understand and figure out if a substance is an agonist or antagonist Side Effects – additional physiological or psychological effects of a drug beside the one intended- Often arise because neurotransmitters are used in many different places throughout the brain and body- Side Effect Examples – SSRI’so Selective Serotonin Reuptake Inhibitors – prevent reuptake of serotonin after release to the synapse by serotonergic neuronso Prescribed for depression due to low levels of serotonin in depression Serotonergic neurons also project to brain areas regulating sleep and food intake so changes in arousal and appetite also occur Serotonin also influence gut motility so nausea can also be aside effect of SSRI’so How are Drugs Cleared from the Body?? 4 Methods of Drug Clearance- Metabolism – often by the liver (MAIN)- Elimination – by kidneys or gut (MAIN)- Sequestration – in fat or other cells or fluid compartments- Degradation and Uptake – by neurons or glia cells- Drug Addiction – persistent use of a substance despite problems related to the use of the substanceo Characteristics of Addiction Tolerance – need to increase dosage just to maintain the results/ initial high- Metabolic or Pharmacokinetic – an increase in the number of enzymes breaking down a drug in the liver, blood, or braino Up-regulation of enzymes in the liver or other organs that degrades the drug or substanceo Increased clearance via kidneys or gut Ex – alcohol dehydrogenase in alcoholics- Cellular or Pharmacodynadmic – response to the drug is decreased at the neurono Decreased post synaptic receptor density (most common)o Increased uptake or inactivation by neurons and gliao Changes in dendritic branching and/or synaptic number between affected neurons with chronic drug use Cellular tolerance is a form of learning and memory- Behavioral of Psychological – behavioral adaptations to the effects of a drugo Behavioral Adaptation – ability to act unaltered by high levels of drug because of repeated use and familiarity with the effects of the drugo Learned Tolerance – preforming a task when under the influences ofa substance improves performance of the task when under the influence of the substanceo Environmental-Dependent Tolerance – the development of tolerance to alcohol’s effects over several drinking sessions is accelerated if alcohol is always administered in the same environment or is accompanied by the same cues Dependence – the need to continue to use and/or unsuccessful efforts to reduce or control use of a drug or substance- Associated with symptoms of withdrawal upon cessation or reduction of dosage Withdrawal – group of symptoms (physical and psychological) that occurs upon discontinuation or decrease in the intake of the drug- Physical Symptomso Sweatingo Rapid HeartRateo Nausea andvomitingo Headacheo Chillso Feverso Changes in appetiteo Changes in sleep patternso Cramps-- Psychological Symptoms o Irritability and mood swingso Depressiono Angero Restlessnesso Fatigueo Memory problemso Delusionso Hallucinationso Paranoia- 6 Drugs commonly causing withdrawalo Caffeineo Nicotineo Alcoholo Cannabiso Opiates – heroino Benzodiazapines – thalium (anti-anxiety)- Withdrawal is Related to Toleranceo Changes in synthesis, storage, release, etc., in response to drug use will change responsiveness of the post synaptic neurono If addicted person stops taking the drug, it will no longer have the same effect as it had before they used it as the neurons have now compensated for its presence in high doseso This means that the synaptic transmission is even more different than normal until the neuron changes back to how it was beforeo The magnitude of withdrawal symptoms depends on the extent of the neuron’s compensatory changes to the ever increasing levels of the drug, which in turn depends on how much and for how long we were taking the