NSC 3361 EXAM 4

How are neuromodulators different from agonists and antagonists?

INDIRECT neurotransmitter effects

-X blocks Y which activates Z, X is an antagonist for Y and a neuromodulator for Z.

GABA and glutamate are what type of neurotransmitter?

Amino acid neurotransmitter

Acetylcholine, Dopamine and serotonin are what type of neurotransmitter?

(mono)amine neurotransmitter

What is retrograde transmission and what type of neurotransmitter can do it?

moves in reverse direction (post to presynaptic)

-gas transmitters like CO2 and nitric oxide

What are examples of peptide neurotransmitters?

oxytocin, vasopressin and endorphins

What type of receptor opens an ion channel?

ionotropic

-mostly in muscles

-direct

-AKA ligand gate

What type of receptor initiates a g-protein cascade?

metabotropic

-indirect

The majority of drugs act on [Metabotropic or Ionotropic] receptors.

Metabotropic

What is an exogenous neurotransmitter?

originates from outside of the body

-toxins or drugs

[Metabotropic or Ionotropic] receptors are more common.

Metabotropic

-metabotropic receptors can adapt more easily

How does a partial agonist compare to a full agonist?

less efficacy

How does a noncompetitive antagonist compare to a competitive antagonist?

competitive antagonists directly block binding site for transmitters

-noncompetitive antagonists bind somewhere else on the receptor

What neurotransmitter is released at the neuromuscular junction and what receptors does it bind to?

Acetylcholine (Ach)

-Muscarinic and Nicotinic

Curare is an antagonist for?

acetylcholine through nicotinic receptors

Atropine binds to what receptor?

Muscarinic receptors

Where is Acetylcholine produced?

basal forebrain

What is nicotine an agonist for?

acetylcholine

-both act on nicotinic receptors

What are properties of nicotinic receptors?

ionotropic

-PNS

-Excitatory

what are properties of muscarinic receptors?

metabotropic

-CNS

-Excitatory or Inhibitory

Where does nicotine bind to in the brain?

ventral tegmental area

-nicotinic ACh receptors

Caffeine excites catecholamine through what molecule to enhance alertness?

adenosine

-caffeine is a neuromodulator (indirect) for catecholamine

What does adenosine do?

induces sleep

What are the difference in how nicotine effects the PNS and CNS

PNS: muscle twitching

CNS: alertness

What are some examples of catecholamines?

dopamine, norepinephrine, epinephrine

What part of tobacco makes it addictive?

nicotine

-damage to health comes from other parts of tobacco

What does cocaine do in synaptic cleft?

blocks reuptake of dopamine by blocking monoamine transporter

Caffeine is an antagonist for?

Adenosine

-competitive

What is CART

cocaine-amphetamine-regulated transcript

-peptide for pleasure and appetite supression.

What effects does chronic cocaine use have?

downregulation of metabolism

-less dopamine release

-similar to alzheimers

What do amphetamines do in synaptic cleft?

block re-uptake and increase release of catecholamines

-short term alertness and stamina

-long term loss of sleep and schizophrenic symptoms

What condition can amphetamines help treat?

ADHD

-increase activity for executive function (prefrontal and cerebellum)

-stimulate inhibitory networks for impulse control

What are some examples of drugs that can help combat ADHD?

Adderall/dextroamphetamine

Ritalin/methylphenidate

Strattera/atomoxetine

-amphetamine-like drugs

Cortico-thalamic network is stimulated by what type of medication?

ADHD medication/Amphetamines

-increase attention, reduce impulses

What are drugs that reduce pain called?

analgesics

Where are endrophins produced?

pituitary and hypothalamus

What are the three endogenous opiates?

Dynorphins, Enkepalins, and Endorphins

-produced during excitement/pain

Locus coeruleus and periaqueductal gray (PAG) have a high quantity of what type of receptor?

opiate receptors

-morphine binds here

Anandamine and 2-AG bind to what type of receptor? Where are these chemicals from?

cannabinoid receptors

-endocannabinoids: produced in body

Why can Anandamine and 2-AG not be stored for use?

lipophilic nature means they can't be stored in vesicle

-produced on demand

Endocannabinoids are [Anterograde or Retrograde].

Retrograde

Impaired short term memory, Slow reaction time, euphoria and calmness are associated with what type of drug?

Cannabinoids

Why is alcohol biphasic?

Low dose alcohol is a stimulant, but high dose alcohol is sedative

What effect does alcohol have on metabolism?

reduces metabolism

What receptor does alcohol act on? What neurotransmitters are impacted?

Acts on GABAa receptor to increase GABA binding

-glutamate inhibited

-dopamine, opiate, serotonin and cannabinoid receptors stimulated

Why are seizures a symptom of alcohol withdrawal?

glutamate receptors increase in response to constant inhibition

-suddenly stopping alcohol causes oversensitivity

What areas of the brain are impacted through chronic alcoholism?

Cerebellum and frontal lobe

How does drinking alcohol during pregnancy impact fetal development?

Neuronal migration fails

-smaller brain

What is MDMA/LSD an agonist of?

serotonin

What area of the brain does MDMA/LSD act on?

visual cortex

Why is MDMA/LSD not addictive?

does not act on Ventral Tegmental Area (VTA)

-no dopamine interaction

What neurotransmitter does MDMA/LSD act on?

excess serotonin release

-also oxytocin release

How does MDMA act on serotonin?

blocks the reuptake transporter

-this keeps serotonin in synaptic cleft

Phencyclidine (PCP) acts on what receptor/neurotransmitter?

NDMA receptor

-PCP inhibits glutamate

Detachment from reality, catatonia and combativeness are symptoms of what drug?

Phencyclidine (PCP)

What are some effects from the over-stigmatization of drugs?

-Justify police brutality

-Most drugs are not as abusive as it seems

-Drugs do not cause brain damage in imaging studies

What pathway do addictive drugs act on?

Mesolibocoritical dopamine system.

-increased dopamine release in addiction

What constitutes addiction?

doing something compulsively despite knowledge of harmful consequences

-ability to resist falls over time

Tolerance [Increases/Decreases] while taking a drug and sensitization [Increases/Decreases].

increases, decreases

What happens to receptors in drugs that cause up-regulation/sensitization?

more receptors become available

-nicotine

What happens to receptors in drugs that cause down-regulation/tolerance?

fewer receptors available

-beznodiazepines

What is withdrawal?

distress following discontinuing use of an addictive drug

Physical dependence is cause by?

withdrawal symptoms

-not the main reason behind addiction

What structure in the VTA releases dopamine?

nucleus accumbens

-located in medial foreman bundle

What is the physical difference between addiction and withdrawal?

Addiction is in the VTA; Withdrawal is in the PAG

What protein causes high relapse rates in people who have used cocaine?

delta FosB

-perpetuates craving in nucleus accumbens

-remains for years after first usage

How do agnostic drugs treat addiction?

mimic the drug's effects but milder

-(partial) agonists

-helps motivation

What agnostic drugs are used to combat opiate and nicotine addictions?

-Methadone or Buprenorphine for opiates

-Nicotine patch or Chantix/varenicline for nicotine

Naltrexone and Baclofen are what type of drugs?

Antagonistic treatments for addiction

-naltrexone for opiate

-baclofen for alcohol

How do antagonistic drugs combat addiction?

block drug effects

-interfere with dopamine production

How can antagonistic drugs be less effective than agnostic drugs for addiction treatment?

antagonistic drugs rely on the patient's motivation to quit

What is Antabuse/disulfiram used for?

treat alcoholism by creating an aversion feeling when taking alcohol.

How could potential anti-drug vaccines work?

antibodies could degrade or block the target drug from reaching receptors

What is the key symptom of schizophrenia?

dissociative thinking or impaired logical thought

What is the difference between a positive and negative symptom?

-positive symptoms cause something to be gained

-negative symptoms cause something to be lost

What are positive symptoms of schizophrenia?

hallucinations

delusions

excited motor behaviors

-will respond better to medication

What are negative symptoms of schizophrenia?

slow thought and speech

-emotional and social withdrawal

-blunted affect or emotional expression

When are most people diagnosed with schizophrenia?

20's

-avg is 26

What can cause identical twins to have different outcomes from a heritable disease?

Vulnerability model

-environment changes gene expression

-same genome but different phenotype

What is the winter birth effect?

higher rate of schizophrenia in people born in the winter

-supports vulnerability model

How do gray matter and ventricles vary in schizophrenic patients?

less gray matter

-less mass usually leads to larger ventricles, but not everyone

Pyramidal cells in what brain structure are altered in schizophrenia?

hippocampus

-pyramidal cells become disorganized

What does a deficiency in Reelin cause in schizophrenics?

Reelin is a control signal for stopping neuronal migration in hippocampus and prefrontal areas

Temporal and frontal lobes of the brain show [Higher/Lower] activity in schizophrenics.

lower

What are neuroleptics?

anti psychotics with major inhibition effects

What does a typical neuroleptic do?

dopamine antagonist

-treats schizophrenic and aggressive behavior

What do atypical neuroleptic drugs do?

serotonin and dopamine antagonists

-also decrease glutamate reuptake

-some increase dopamine in frontal cortex

What is the dopamine hypothesis of schizophrenia?

schizophrenia is caused by an excess of dopamine release or dopamine receptors

What are flaws with the dopamine hypothesis of schizophrenia?

-receptors are blocked quickly, symptoms removed slowly

-schizophrenics have normal DA metabolization levels

-some neuroleptics increase dopamine levels

Symptoms of what disease can originate from anti-dopamine drugs used for schizophrenia?

parkinsons

-parkinsons is treated with increased dopamine, which can lead to schizophrenic symptoms

Clozapine, Trazodone, Chlorpromazine and Promazine can all be used to treat what condition?

Schizophrenia

What is the glutamate hypothesis of schizophrenia?

Schizophrenia is due to underactivation of glutamate receptors

How are PCP and schizophrenia related?

PCP inhibits glutamate

-chronic PCP use can lead to acute schizophrenic symptoms

Abilify/aripiprazole and Risperdal/risperidone belong to what class of drugs?

atypical neuroleptics

What is the endocannabinoid hypothesis of schizophrenia?

Endocannabinoid levels are raised in the CSF of schizophrenics

-CB1 receptors activated by ECs inhibit other neurotransmitters and can cause schizophrenia

What are some symptoms of depression?

-Loss of interest or pleasure

-Fatigue

-Weight change

-Concentration problems

-Sleep change

How is clinical depression different from normal depression?

-normal depression happens to everyone and lasts hours-days and does not impair function

-clinical depression debilitates function and lasts for weeks to months

How does blood flow in the brain change in patients with depression?

Increased: orbitofrontal and amygdala

-concern and fear

Decreased: areas of attention and language

What are the monoamine neurotransmitters?

dopamine, epinephrine, norepinephrine, serotonin

What protein breaks monoamines down?

monoamine oxidase

What class of drugs prevent the breakdown of monoamines?

MAOIs

-monoamine oxidase inhibitors