PSYC 30 Chapters 5-7 Notes
PSYC 30 Chapters 5-7 Notes PSYC 309
Popular in Psychopharmacology
verified elite notetaker
verified elite notetaker
verified elite notetaker
verified elite notetaker
verified elite notetaker
SPHU 1010 (Public Health, Lorelei Dickey-Cropley, Intro to Public Health)
verified elite notetaker
Popular in Psychlogy
This 14 page Bundle was uploaded by Stacey Kane on Tuesday March 29, 2016. The Bundle belongs to PSYC 309 at Towson University taught by Paul Pistell in Spring 2015. Since its upload, it has received 28 views. For similar materials see Psychopharmacology in Psychlogy at Towson University.
Reviews for PSYC 30 Chapters 5-7 Notes
Report this Material
What is Karma?
Karma is the currency of StudySoup.
You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!
Date Created: 03/29/16
Catecholamines o Dopamine (DA) Dopaminergic o Norepinephrine (NE) Noradrenergic o Epinephrine (EPI) Adrenergic o Monoamines Synthesis o Multi-step pathway Regulate NT availability Precursor: the more the precursor the more the NT Blockade: NT level are lowered o TH is rate limiting enzyme Regulated by: DA and NE levels: if there’s enough the system says to stop production Rate of cell firing: the faster its firing the more active TH is to help create more NT o Drugs L-DOPA: drug used to help a psychiatric condition; increases level of dopamine Alpha-methyl-para-tryosine (AMPT): TH blocker (reverses efficacious antidepressants) Storage and Release of Catecholamines o Vesicles Prepackaged amount Degradation protecting o Vesicular monamine transporter (VMAT) VMAT1: adrenal medulla VMAT2: brain Transport synthesixed NT to vesicle o Drugs Reserpine: VMAT1 and VMAT2 blocker Animals- sedation Humans- depressive symptoms NE and DA cannot be released from vesicle L-DOPA reverses: creates precursor for dopamine Amphetamine Releases NE and DA independent of cell firing: no action potential has to arrive Increases locomotion Stereotyped behaviors: purposeless movements that are repeated over and over Catecholamines and Autoreceptors o NE and DA: many receptor subtypes o D2 and Alpha2 are autoreceptors Activation reduces Ca2+ entry Agonists: even if there isn’t too much it will still stop release of NT Antagonists: block auto-receptor and doesn’t stop release of NT o Opioid withdrawal Activated NE system: increased heart rate, blood pressure and diarrhea To treat: release agonists at auto receptor; symptoms are blocked o Clonidine (alpha2, agonist) o Yohimbine (alpha2 antagonist) NE and anxiety Yohmibine: can trigger panic attacks, increases anxiety Catecholamine Inactivation o Two processes Reuptake by DA and NE transporters Drugs (blockers) Tricyclic antidepressants: NE and 5-HT Reboxetine: NE Atomoxetine: NE Cocaine: DA, NE and 5-HT o Metabolic Breakdown Enzymes: COMT and MAO Metabolites DA: homovanillic acid (HVA) NE: MHPG; VMA PNS You can increase or decrease the breakdown Drugs: Phenelzine and tranylcypromine: MAO inhibitors (MAOIs): depression Entacapone and tolcapone: COPT inhibitors – L-DOPA supplementation Dopaminergic Systems o Catecholamine classification system A1-A7: noradrenergric A8-A16: dopaminergic o Nigrostriatal tract SN to caudate-putamen (striatum) Control of movement o Mesolimbic: from midbrain to cortex and limbic system o Mesocortical: from midbrain to cerebral cortex and hippocampus Schizophrenia Drug abuse Nigrostriatal Damage o Two toxins: MPTP: will cause a person to get full blown Parkinson’s in a short time 6-OHDA Specific for catecholaminergic neurons Bilateral lesions o Sensory neglect o Motivational deficits: won’t go for food or water, no motivation o Motor impairment: not complete Unilateral lesion o Postural asymmetry: one side of the body works and the other doesn’t work at all o Will only happen if you have stroke, will not happen on its own DA Receptor Subtypes o D1-d5 all metabotropic o D1 and D2 in striatum and nucleus accumbens D2 also postsynaptic receptor o Opposite effects on adenylyl cyclase D1 increases D2 decreases o Work through different G proteins (G1 and G2) o Changes in cAMP alter excitability of cell DA Receptor Agonists and Antagonists o Agonists: increases behavior Apoorphine – D1 and D2 = behavioral activation SKF 38393 – D1 = elicits self-grooming Quinpirole – D2 and D3 = increases locomotion and sniffing o Antagonists: decreases behavior Haloperidol – D2 = catalepsy SCH 23390 – D1 = catalepsy D2 antagonists used for schizophrenia DA Knockout Mice o Mice lack the gene for TH in dopaminergic neurons o DA missing KO mice lacking the DA transporter o Hyperactivity: DAT mice cannot clear S o Reduced response to cocaine and amphetamine D1 and D2 KO Mice o D1 receptor Reduced growth and death without moistened food Increased locomotor and reduced habituation Motor coordination deficits Exhibit cognitive deficits o D2 receptor Impaired spontaneous movement Impaired coordination Impaired postural control Degree of impairment dependent on background strain o Both rd Fatality by 3 week Cannot be rescued by L-DOPA o D1= increase activity level o D2= decrease activity level D3-5 KO mice o Not studied as extensively o D3- complex behavior changed Impaired ability to inhibit behavioral response in novel situations Failure to stop a behavior o D4 and D5- little apparent behavioral effects D4: differ in response to psychoactive drugs o Physiological effect: D2: elevated prolactin levels Any DA receptor: hypertension via dysregulation of salt balance and blood pressure Ethanol and DA KO mice o Ethanol can produce either locomotion stimulation (low doses) or sedation (higher doses) o D2 and D4- enhanced locomotor stimulation o D2- blunted ethanol-induced sedation o D1 and D2- reduced voluntary ethanol consumption Reward pathway Didn’t see ethanol as rewarding so they didn’t take more o A single transmitter, acting through different receptor subtypes May influence many different behaviors and physiological functions May play a complicated role in responses to psychoactive drugs Locus coeruleus (LC) and NE projections o NE also plays a critical role in the PNs Sympathetic branch of ANS (NT) Adrenal gland (hormone) NE in blood cannot enter brain: NE stays in the area in which they are and do not cross into the other Adrenergic Receptor subtypes o All metabotropic o Mediate both NT (mainly NE) and hormonal (mainly EPI) o Alpha1 A, B, D, L: phospholipase C (PLC) and increase Ca2+ o Alpha2 A, B, C: decrease adenylyl cyclase = decrease cAMP and Ca2+ o Beta1,2,3,4: increases adenylyl cyclase and Behavioral Implication Arousal o Injection of NE into LC promote arousal o LC neurons fire more rapidly when awake o NE increases time awake o Injections into medial septal area Phenylephrine (alpha1 agonist) Isoproterenol (beta agonist) Behavioral Implication Consolidation of Emotional Memories o One-trial passive avoidance (emotional learning) Increase EPI, glucocorticoids, CNS NE o Weak shock and EPI 0-10 minutes after but not later increased latencies Increase in EPI is attached to the emotional memory o Later studies: Implicated NE, glucocorticoids and other NTs in amygdala Nonpsychiatirl Conditions o Beta agonist (albuterol): asthma o Alpha1 agonist (phenylephrine): colds and allergies o Alpha2 agonist (clonidine): hypertension o Alpha2 antagonist (yohimbine): impotence o Alpha1 antagonist (porzasin): hypertension o Beta antagonists (propranolol and metaprolol): hypertension and anxiety Keep heart rate at a steady pace in order to prevent a panic attack Serotonin (5-HT) o Popular culture o Synthesis (two steps) Tryptophan: from dietary amino acids Tryptophan to 5-HT is rate limiting step Tyrptophan and the BBB o Fernstrom and Wurtman (1970s) Fasted rates and fed protein rich meal Typtophan blood levels elevated but not brain levels Proteins contain more large amino acids Ratio is critical Fasted rats and high carbohydrate diet Carbs trigger insulin and stimulate diet o Carbs trigger insulin and stimulate uptake of most amino acids from blood except tryptophan o Ratio is increases o Increased brain levels Humans show similar results, but not as large Rapid tryptophan depletion and depression relapse o PCPA Irreversibly inhibits tryptophan hydroxylase 80-90% of 5-HT reduction for up to two weeks o Humans can be given a cocktail of amino acids without tryptophan o Leads to return of depressive symptoms 5-HT storage, release and inactivation o VMAT2- transports 5-HT into vesicles Reserpine: VMA blocker o 5-HT1B or 5-HT1D terminal autoreceptors Inhibit 5-HT release o 5-HT agonists Para-chloramphetamine Fenfluramine MDMA o Inactivation 5-HTtransporter (SERT) and SSRIs Metabolized by MAO into 5-hydroxyindoleacetic acid (5-HIAA) SERT KO mice MDMA o More potent effect on 5-HT o Initially used therapeutically o High doses deplete forebrain 5-ht and loss of serotonergic axons o Effective for severe treatment-resistant PTSD at low, controlled doses in therapeutic setting Anatomy of the Serotonergic System o Dorsal and median raphe nuclei o Innervate virtually all forebrain areas Serotonin Receptor Subtypes o 14 subtypes o M-HT1A: metabotropic (decreases adenylyl cyclase: decreases cell activity) o M-HT2A: Metabotropic (increases PLC: increases cell activity) o All are metabotropic except for 5-HT3 which is ionotropic 5-HT1A o Many brain areas Hippocampus, septum, amygdala, and dorsal raphe o Located postsynaptically Inhibit adenylyl cyclase and therefor decreases cAMP Open K+ channels Decreasing second messengers and takes it father away from an action potential o Agonists Buspirone, ispapirone, 8-OH-DPAT o Antagonist WAY 100635 5-HT2A Receptors o Cerebral cortex Striatum, nucleus accumbers, and others o Located postsynaptically Phosphoinositide (increases Ca++ and increases PKC) o Agonist DOI: “head twitch” response and hallucinations LSD: appears to stimulates receptors o Antagonist Ketansein and ritanserin Clozapine and risperidone (also effect DA; antipsychotics with reduced motor disturbances) Other Receptor Subtypes o Widespread expression in nervous system and non-neural tissues o 5-HTaB and 5-HT1D and migraines Abnormal dilation of blood vessels = migraines Agonists (triptans) constrict blood vessels to treat migraines o 5-HT3 nausea and vomiting Located on peripheral terminals of vagus nerve Transmits sensory info from GI tract to brain Chemotherapy drugs and radiation release f-HT in gut, stimulate 5-HT3 receptors and cause vomiting Makes you not want to eat Antagonists counteract: taken before chemo, will reduce vomiting Behavioral and Physiological functions of 5-HT o In humans Correlate CSF 5-HIAA or post-mortem regional 5-ht and 5-HIAA concentrations with behavior or disorders Assess behavioral, subjective and physiological responses to 5- HT challenges (agonist, antagonists, SSRIs) Can be injected into system and then observe how behavior is effected Association between psychiatric disorders and polymorphisms in SERT or other receptors Do people have mutations in these receptors? Do these mutations effect behavior? Animal Studies o Mice born missing serotonergic neurons: do not create any serotonin Will survive, but significant mortality If they make it past 30 days, they will survive Thermoregulation difficulties (when placed in the cold) Long episodes of apnea: if given DOI, it comes back just not in the same way o Hunger and eating Hypophagia: not eating enough, appetite depressants H-HT1B of 5-HT2C agonists, 5-HT6 antagonists Hyperphagia: increased appetite 5-HT1A agonists o Anxiety 5-HT1A agonists decrease anxiety 5-HT1A KO mice exhibit increased anxiety 5-HT2A and 5-HT2C agonists increases anxiety 5-HT2A or 5-HT2c KO mice exhibit decreases anxiety o Pain Implicated in pain processing at level of spinal cord Hypoalgesia mediated by 5-HT1B and 5-HT3: reduces pain However, under some conditions 5-HT3 activation leads to hyperalgesia o Learning and Memory o Powerfully influenced by various agonists and antagonists Pre-training 5-HT1A agonist (8-OH-DPAT) impair contextual fear conditioning and memory Similar effects with 8-OH-DPAT into hippocampus Blocked by prior infusion of 5-HT1A antagonist (WAY 100635) 5-HT4 partial agonists enhance learning and memory 5-HT5 antagonists facilitate memory on several tasks o Serotonin relates to learning and memory 5-HT and Aggression o Human aggression: intent is important Premeditated: planned Impulsive: frustration or threat o Animals: must operationalize o Neural circuitry has been outlined in humans and animals o All of the brains areas receive substantial serotonergic innervation Correlate CSF 5-hIAA with aggression Increase 5-HT via SSRI administration or SERT KO mice Decrease 5-HT via tryptophan hydroxylase inhibition or 5-HT neurotoxin o Overall, relatively higher levels of serotonin is associated with less aggression and lower levels of serotonin are associated with higher levels of aggression 5-HT1A and 5-HT1B agonists decreases aggression 5-HT1B KO mice exhibit increased aggression o Might be working on other NT systems o Could be influences impulsivity Prefrontal cortex balance 5-HT2A (high activity increases impulsivity) and 5-HT2C (high activity decreases impulsivity) o Rhesus monkeys and 5-HIAA Taken four years previously Measured levels of 5-HIAA, and then four years later saw who was dead and who was alive Those with lower levels were much more likely to get in fights and be aggressive and more were dead, those with high levels were much more likely to be alive o Human violence and aggression are serious social problems o Low levels of 5-HIAA in the CSF Aggression and antisocial behavior (assault, arson, murder, and child abuse) o Aggression and 5-HT agonists Fluoxetine (SERT antagonist (boosted levels of serotonin) : decreased irritability and aggressiveness Behavioral Effects of 5-HT (serotonin syndrome) o If endogenous tome of 5-HT is increases (either by providing pre- cursor, blocking MAO or with some agonists) a characteristic behavioral syndrome is produced. That syndrome includes: Rats: Fore par treading (piano playing) Straub tail Hind limb abduction Rigidity Head shaking Resting tremor Salivation o Human Serotonin Syndrome Hyperserotonergic state Can be fatal Death can be rapid Increased incidence since 1960s o If serotonin is only available below the raphe nuclei, you can still get serotonin syndrome o There are 5-HT terminals on motor neurons o If we record from a motor nucleus from a rat and apply glutamate, we observe an increase in unit firing o If we then apply 5-HT alone, we see no effect on unit firing o If we apply both 5-HT and glutamate we see a marked increase in unit firing o 5-HT modulates firing at motor neurons Acetylcholine (ACh) o Curare o ACh: life sustaining, but deadly If you don’t have enough you die, but if you have too much you die o Only synthesized by a small number of neurons (cholinergic) Synthesis of ACh o Formed in a single step Choline: in diet and liver Acetyl CoA: metabolism of sugar and fats in cells ChAT only found in ACh neurons Choline + Acetyl CoA = ACh o Rate of synthesis Availability of precursors: more precursors means more ACh Rate of cell firing: more firing means more ACh o Decreased ChAT??? o Increased choline and Alzheimer’s disease gave no improvement Cholinergic Synapse o Couple thousand per vesicle o Vesicular ACh transporter (VAChT) o Drugs Vesamicol – VAChT blocker Black widow venom increases PNS ACh release: more is released into synapse Leads to sweating, nausea, pain, salivation, tremors Botulism decreases/prevents ACh release Paralysis ACh Metabolism o AChE carefully controls ACh levels Presynaptic: excess ACh levels Postsynaptic: released ACh levels Muscle cells secrete AChE o Choline undergoes reuptake o Choline transporter KO mice Die within one hour Choline pulled back into cell is very critical for body to know levels of ACh o Drugs Hemicholinium3 (HC3): choline transporter blocker: reduces amount of ACh where levels of other NT would increase Physostigmine (isolated from Calabar beans): blocks AChE: levels of ACh increase Slurred speech, mental confusion, hallucinations, loss of reflexes, convulsions, even coma and death Botulinum Toxin – Deadly poison, Therapeutic Remedy, and Cosmetic Aid o Human lethal dose: 0.3 micrograms o Interferes with ACh release at neuromuscular junctions o Therapeutics Strabismus: cross eyes Blepharospasm: eye spasms Hemi facial spasm: half the face spasms Spastic cerebral palsy Dystonias o Botox Myasthenia Gravis o Autoimmune disorder Antibodies for muscle ACh receptor Receptor downregulation (less sensitivity) o Muscle weakness and fatigue o Neostigmine and pyridostigmine Synthetic physostihmine analogs (do not cross blood brain barrier) Less AChE (enzyme that metabolizes ACh) increases ACh activity Stress, pyridostigmine and the brain o Sarin and Soman Irreversible AChE inhibitors Nerve gas o Pyridostigmine bromide (PB) Reversible AChE inhibitor protects AChE from permanent inactivation by nerve gas Low blood brain barrier penetration o Stress and the blood brain barrier Mice given forced swim test Ten minutes later various doses of PB Stress temporarily unblocks the blood brain barrier Found that PB was getting into the unblocked BBB o Gulf War Syndrome ACh Synapses in the Parasympathetic and sympathetic ANS o ACh is widely involved in neuromuscular and autonomic systems o Drugs that interfere with ACh extremely powerful and can be toxic Brain cholinergic Pathways o Basal forebrain cholinergic system (BFCS) cognition o Balance between ACh and DA in striatum contributes to PD motor symptoms o Dorsolateral pons substantia nigra (nicotinic receptors) Brainstems and thalamic areas (arousal, sensory processing, and initiation of REM Cholinergic Interference o Atropine and scopolamine: ACh muscarinic receptor and antagonist o 192lgGsaporin: neurotoxin specific for BFCS ACh neurons o Signal detection task o May be more attentional ACh Receptor Subtypes o Two families: stimulated by alkaloids Nicotinic Muscarinic Nicotinic o Neuromuscular junctions in ANS and certain neurons o Ionotropic o Na+ and Ca++ enter (increase excitability) o Fast excitatory response in CNS and PNS o Located pre and postsynaptically o 5 subunits (variations produce subtypes) Both alpha units must be activated o Desensitization Continuous stimulation = desensitization Channels remain closed Depolarization block: if long enough, resting membrane potential lost and only restored when agonist removed Succinylcholine (ACh agonist): powerful muscle relaxant resistant to AChE Dtubocurarine (peripheral nicotinic receptor antagonist): blocks Active ingredient in curare Muscarinic o Five subtypes (m1M5) o All metabotropic Some activate phosphoinositide Some inhibit cAMP Some stimulate K+ channels o Widely distributed Brain Neocortex and hippocampus (cognition) Striatum (motor function) M5 KO mice and opiate reward: didn’t show conditioned place preference unless it was a high enough dose; mice who are addicted do not go through withdrawal PNS M2 Cardiac heart muscle decreases heart rate M3 smooth muscle of organs increases Secretory responses: regulating glucose and insulin o Compounds: Agonists: parasympathomimetic agents Muscarine from Amanite muscaria Pilocarpin from Pilocarpus jaborandi Arecoline seeds of the betel nut palm o Ingestion leads to salivation, sweating, pinpoint pupils, severe abdominal pain, strong smooth muscle contraction and painful diarrhea Antagonists: parasympatholytic agents Atropine from deadly nightshade Scopolamine from henbane o “twilight sleep” you’re awake but you don’t remember anything
Are you sure you want to buy this material for
You're already Subscribed!
Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'