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***PSYCH 275- Brain & Behaviour > Chapter 5 - Neurotransmitters & Drugs > Flashcards

Chapter 5 - Neurotransmitters & Drugs Flashcards

1
Q

Who was Otto Loewi (1921)?

What is acetylcholines role?

A

First isolation of a CHEMICAL MESSENGER

Frog heart experiment

Acetylcholine: works in peripheral and central nervous systems (activates skeletal muscles in SNS, excite or inhibit internal organs in ANS)

Continuing research…

Epinephrine (adrenaline) fight or flight
- hormone to mobilize body as neurotransmitter in CNS

Norepinephrine (noradrenaline)
- brain and parasympathetic in ANS
- accelerates heart rate

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2
Q

What are neurotransmitters?

Give definition W/IN CNS and OUTSIDE CNS

A

Within CNS…
- chemical released by a NEURON onto a target w/ a excitatory or inhibitory effect
- distinctive shape that’s allow them to interact w/ distinctive receptors

Outside CNS…
- chemicals circulate in bloodstream as HORMONES
- action slower than neurotransmitters
- distant/widespread targets

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3
Q

What is the chemical synapse?

A

Junction where neurotransmitter are RELEASED from one neuron to EXCITE or INHIBIT the next

Most synapses in mammalian nervous system are CHEMICAL

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4
Q

What is the presynaptic membrane?

A

Where the action potential TERMINATES to RELEASE the chemical message

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5
Q

What is the postsynaptic membrane?

A

RECEIVING side of the SYNAPSE, where EXCITATORY/INHIBITORY postsynaptic potentials are GENERATED

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6
Q

What is the synaptic cleft?

A

GAP where neurotransmitters travel from presynaptic to postsynaptic membrane

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7
Q

What is the tripartite synapse?

A

FUNCTIONAL INTEGRATION and physical proximity of the presynaptic membrane, postsynaptic membrane and their association w/ astrocytes

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8
Q

What is the anterograde synaptic transmission?

A

PROCESS that occurs when a neurotransmitter is RELEASED from a presynaptic neuron and BINDS to a receptor on a postsynaptic neuron

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9
Q

What are the 5 steps in neurotransmission?

A
  1. Neurotransmitter synthesized inside the neuron
  2. Packaged/stored w/in vesicles at the axon terminal
  3. Transported to presynaptic membrane and released into cleft due to an action potential
  4. Binds to & activates receptors on the postsynaptic membrane
  5. Degraded/removed to deactivate it
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10
Q

What is step 1 (neurotransmitter synthesis)?

A

In axon terminal & cells body

Origins of neurotransmitters:
Peptide
Lipid
Gaseous
Ion

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11
Q

What is step 2 (neurotransmitter storage)?

A

Synaptic vesicle: small MEMBRANE-BOUND spheres that contain one or more neurotransmitter

Storage granule: membranous compartment that holds SEVERAL vesicles containing neurotransmitters

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12
Q

What is step 3 (neurotransmitter release)?

A

At terminal, action potential OPENS voltage-sensitive Ca channels

Ca enters terminal and BINDS to protein calmoduin = form COMPLEX

Complex causes some vesicles to EMPTY their contents into SYNAPSE & others to empty their contents
^^^EXOCYTOSIS

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13
Q

What is step 4 (neurotransmitter binding)?

4 TYPES OF RECEPTORS INVOLVED

A

Transmitter-activated receptors:
- protein embedded in membrane of a cell that has a BINDING SITE for a spec neurotransmitter

Iontropic receptor:
- associated w/ pores open to allow IONS into membrane
*excititory: Na in
*inhibitory: K out or Cl in

Metabotropic receptor:
- embedded membrane protein w/ a BINDING SITE for a neurotransmitter linked to a G protein

Autoreceptor:
- self-receptor in a neuronal membrane, responds to same transmitter released by neuron
- part of a (-) feedback loop allowing neuron to adjust its own input
- can be iontropic or metabotropic (rare)

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14
Q

What is step 5 (neurotransmitter deactivation)?

4 DIFFERENT WAYS

A

Diffusion: spreads out into extra cellular enviro AWAY from synaptic cleft

Degradation: ENZYMES in synaptic cleft BREAK down the neurotransmitter

Reuptake: brought BACK into presynaptic axon terminal (by-products of degradation)

Astrocyte uptake: nearby astrocytes TAKE UP neurotransmitter, can also store them

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15
Q

What are second messengers?

A

Bind to a membrane-bound channel

Alters ion flow

Initiate a rxn incorporating intracellular protein molecules into the cell membrane

Bind to sites on cells DNA to INITIATE/CEASE produc of spec proteins

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16
Q

What are synapse variations?

A

Synapse VARY in location, structure, fxn, and target

CONNECTIONS to the dendrites, cell body, axon of a neuron - transmitters can CONTROL the actions of the neuron in varies ways

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17
Q

What is a gap junction?

A

Electrical synapse where 2 neurons intracelluar fluids come into DIRECT CONTACT

Eliminates the DELAY in information flow in chemical synapse (~5ms saved)

Forms when CONNEXIN proteins in one cell membrane connect to a HEMICHANNEL in an adjacent cell membrane

Allows ions to flow b/w the two membranes

GATED CHANNELS

Can vary in pore size (allows for selectivity)

Can be part of “mixed synapses” allows for chemical and electrical synaptic transmission in combo

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18
Q

What is an excitatory synapse?

A

Typically located on DENDRITES

ROUND vesicles

DENSE material on membranes

WIDE cleft

LARGE active zone

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19
Q

What is an inhibitory synapse?

A

Typically located on CELL BODY

FLAT vesicles

SPARSE material on membranes

NARROW cleft

SMALL active zone

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20
Q

What counts as a neurotransmitter?

A

CARRIES an message from one neuron to another by influencing the VOLTAGE on the postsynaptic membrane

Changes the STRUCTURE of a synapse

Communicates by sending MESSAGES in the OPPOSITE DIRECTION

***(retrograde) influence the release/reuptake of transmitters of the PRESYNAPTIC SIDE

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21
Q

What are 5 different classes of neurotransmitters?

A
  1. Small-molecule
  2. Peptide
  3. Lipid
  4. Gaseous
  5. Ion
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22
Q

What are small-molecule transmitters?

A

Class of QUICK-ACTING neurotransmitter

Synthesized in AXON TERMINAL from DIETARY nutrients and packaged ready for use in axon terminals

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23
Q

What are peptide transmitters?

A

SHORT AMINO ACID CHAIN (fewer than 100 aa/s)

Can act as neurotransmitters OR hormones

Usually assembled on neurons RIBOSOMES, packaged by Golgi bodies and transported by micro tubes to axon terminals

Act SLOWLY and are NOT replaced quickly

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24
Q

What are lipid transmitters?

A

Lipids (fatty molecules) ACT as MESSENGERS

Lipids are special in that they can FREELY DIFFUSE through membranes

Makes traditional storage difficult

Ex) endocannabinoids
- act on recoveries at presynaptic membrane (appetite, pain, sleep, ,old, memory, anxiety etc…)

Ex) phytocannabinoids
- obtained from hemp plants

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25
Q

What are gaseous transmitters?

A

NOT stored in or released from synaptic vesicles

SYNTHESIZED in cell as needed

Another one that can EASILY CROSS CELL MEMBRANE

Ex) nitric oxide (NO)
Ex) carbon monoxide (CO)
Ex) hydrogen sulphide (H2S)

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26
Q

What are ion transmitters?

A

Recent evidence has led researchers to CLASSIFY zinc as a transmitter

ACTIVELY TRANSPORTED, packaged into vesicles (usually w/ glutamate) and released into synaptic cleft

***STILL BEING RESEARCHED

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27
Q

What are the cholinergic (motor) neurons in the somatic nervous system?

What is the nicotinic acetylcholine receptor?

A

MOTOR neurons

Main neurotransmitter is ACETYLCHOLINE

EXCITATORY at skeletal muscles
—————————————————————————
Transmitter-activated ionotropic channel

When ACETYLCHOLINE/NICOTINE binds = large pore opens

K flows OUT and Na flows in simultaneously

Muscle fibre depolarizers

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28
Q

In the autonomic nervous system (parasympathetic/sympathetic) both are controlled by “________ ________” that leave the CNS at “_____” levels of the spinal cord

A

Cholinergic neurons; 2

***Can be excitatory or inhibitory depending on what it’s targeting

Ex) gut inhibitory, heart excitatory

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29
Q

What happens to neurotransmitters in the enteric nervous system?

A

Detect mechanical/chemical cond in gastrointestinal system

Can ACT w/out CNS input

Makes use of 30+ transmitters in total, many used also in the CNS

Serotonin and dopamine are important

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30
Q

What happens to neurotransmitters union the CNS?

What are the 4 activating systems?

A

Activating system - neural pathway COORDINATES brain activity through a SINGLE neurotransmitter

  1. Cholinergic
  2. Dopaminergic
  3. Noradrenergic
  4. Serotonergic
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31
Q

What is the cholinergic system?

A

Acetylcholine

Active in MAINTAINING ATTENTION & WAKING EEG PATTERN

Thought to play a ROLE IN MEMORY (neuron excitatory)

Death of these types of neurons and decrease of ACh in neocortex is thought to be related to = Alzheimer’s disease

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32
Q

What is the dopaminergic system?

A

Dopamine

Active in MAINTAINING NORMAL MOTOR BEHAVIOUR

Loss of DA is related to muscle rigidity and dyskinesia in Parkinson’s disease

Mesolithic pathways
- release causes repetition of behaviours
- most affected by addictive drugs/behav addictions
- increase may be related to schizophrenia
- decreases may be related to deficits of attention

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33
Q

What is the noradrenergic system?

A

Norepinephrine

Active in MAINTAINING EMOTIONAL TONE

Decrease in NA activity are thought to be related to depression

Increases are thought to be related to mania

Decreased NE activity is associated with hyperactivity and ADHD

34
Q

What is the serotonergic system?

A

Serotonin

Active in MAINTAINING WAKING EEG PATTERN

Changes in serotonin activity are related to OCD, tics and schizophrenia

Decreases in serotonin activity are related to depression

Abnormalities in brain stem neurons are linked to disorders such as sleep apnea and SIDS

35
Q

What is neuromodulation?

A

Neuromodulaters are neurotransmitters that FACILITATE the 4 activating systems

Includes histamine, several neuropeptides, and endocannaboids

ALTER firing and synaptic characteristics of other neurons

^ typically over longer period of time

36
Q

What are hormones?

What is super important to remember?

A

Secreted by GLANDS in the body and the brain

From feedback loops
- (+) feedback loop: move AWAY from equilibrium (receive signal = increase signal)
- (-) feedback loop: RETURN to equilibrium (receive signal = decrease signal)

***MANY HORMONES ACT AS NEUROTRANSMITTERS, MANY NEUROTRANSMITTERS ACT AS HORMONES

37
Q

Explain the process of neurohormones and the body…

4 STEPS

A
  1. Sensory stimuli
  2. In response, hypothalamus produces NEUROHORMONES that enter the ANTERIOR PITUITARY through veins and the POSTERIOR PITUITARY through axons
  3. On instructions, the pituitary sends HOMRMONES into the BLOODSTREAM to target ENDOCRINE GLANDS
  4. Endocrine glands RELEASE their own hormones that stimulate TARGET ORGANS (including brain)
38
Q

Name 4 hormone classifications…

A
  1. Peptides:
    - insulin, growth hormones, endorphins
  2. Amino acids:
    - melatonin, thyroxine
  3. Lipids:
    - prostaglandin, thrombocytes
  4. Steroids
    - testosterone, cortisol
39
Q

What is involved in the stress-response?

What is the fast response VS the slow response?

A

Physiological and behavioural arousal in an attempt to REDUCE stress

Hippocampus well suited to detecting CORTISOL in the blood and instructing the HYPOTHALMUS to REDUCE cortisol levels

Too much CORTISOL damages neurons in hippocampus

Damaged neurons cannot detect cortisol (cannot act in (-) feedback loop)

  1. Fast response: primes the body immediately for FIGHT OR FLIGHT (epinephrine)
  2. Slow response: both mobilizes the body’s resources to CONFRONT A STRESSOR and REPAIRS stress-related damage (cortisol)
40
Q

What is psychopharmacology?

A

Scientific study of the effects of PSYCHCOACTIVE drugs on the nervous system and behaviour

41
Q

What is a psychoactive drug?

A

Chemical substance that can be introduced to the body to ALTER mood, thought, and behaviour either for MEDICAL purpose or RECREATIONALLY

42
Q

What are different drug routes into the nervous system?

A

Orally & absorbed through the digestive system

Inhaled

Absorbed from a patch to the skin/mucous membrane

Injected into bloodstream into a muscle/brain

43
Q

***REVIEW WHAT METHODS ARE MOST EFFECTIVE TO GET DRUGS INTO BODY

A

.

44
Q

What is the blood-brain barrier?

A

Capillaries OUTSIDE the brain allows DRUGS to move from the BLOODSTREAM to the neighbouring TISSUE fairly easily

Endothelial cells: line INSIDE of capillialries
(Not joined outside the brain, but IN the brain to form tight junctions - hard for substances to pass through)

45
Q

How do astrocytes function in the blood-brain barrier?

A

Allow resources and waste to MOVE b/w BLOODSTREAM & the EXTRACELLULAR FLUID

Their feet WRAP around the brains capillaries to prevent EASY, UNCONTROLLED transmission b/w the 2 fluids

46
Q

How do small molecules and complex molecules move across the blood-brain barrier?

A

Small molecules:
- ex) CO2 & O2
- lipid-soluble molecules that can pass through the ENDOTHELIAL membranes

Complex molecules:
- ex) glucose & amino acids
- carried across membrane by ACTIVE TRANSPORT SYSTEMS & ION PUMPS

***why most of the time we are able to keep things like parasites out of this barrier

47
Q

What are 3 areas in the brain w/out a blood-brain barrier?

A
  1. Pituitary gland:
    - target for many BLOOD-BORNE hormones
  2. Pineal gland:
    - target for hormones that affects CIRCADIAN rhythms
  3. Area postrema:
    - detects and initiates VOMITING of noxious substances
48
Q

How does the body eliminate drugs?

A

Drugs are broken down (catabolized) in the KIDNEY, LIVER, AND INTESTINES

EXCRETED in urine, feces, sweat, breast milk, and exhaled air

Some substances that cannot be REMOVED ex) heavy metal particles, may build up in the body and become TOXIC

49
Q

Compare an agonist VS an antagonist in terms of drug action at the synapse…

A

Agonist:
- substance that ENHANCES the fxn of a SYNAPSE

Antagonist:
- substance that BLOCKS/DECREASES the fxn of a SYNAPSE

50
Q

What are the potential sites of drug action?

5 STEPS/WAYS

A
  1. SYNTHESIS in cell body, axon or terminal
  2. PACKAGING/STORAGE in vesicles
  3. RELEASE from the terminals presynaptic membrane into the synapse
  4. RECEPTOR INTERACTION in the postsynaptic membrane, as transmitter acts on an embedded receptor
  5. (A) INACTIVATION BY REUPTAKE into presynaptic terminal for resuse
    Or…
    (B) INACTIVATION BY ENZYMATIC DEGRADATION of the excess neurotransmitter
51
Q

What is tolerance?

A

LEARNED BEHAVIOUR that results when a response to a stimulus WEAKENS w/ repeated presentations

Driven by body’s attempt to MAINTAIN a state of homeostasis

Decreasing responsiveness to a drug over time

52
Q

What is metabolic tolerance?

A

INCREASE in # of enzymes in the LIVER, BLOOD OR BRAIN used to break down a substance

53
Q

What is cellular tolerance?

A

Activities of BRAIN CELLS adjust to MINIMIZE effects of substance

54
Q

What is learned tolerance?

A

People LEARN TO COPE w/ being intoxicated

55
Q

What is sensitization?

A

INCREASED RESPONSIVENESS to successive doses of a drug

Is an opposite rxn to tolerance

56
Q

What is withdrawal?

A

Occurrence of COMPENSATORY RESPONSES after discontinued drug use

Strong rxns opposite effects of the drug

57
Q

What is learning and tolerance?

A

Environmental stimuli ASSOCIATED w/ drug

Use elicit compensatory responses through CLASSICAL CONDITIONING

58
Q

What is learning and overdose?

A

A NEW ENVIRONMENT will NOT elicit compensatory responses through CLASSICAL CONDITIONING

59
Q

How are drugs categorized? (At least in this class)

A

Based on the neurotransmitter they affect

  1. Chemical
  2. Generic
  3. Branded
60
Q

What are adensinergic antagonists?

Example?

Mode of action?

A

Ex) Caffeine

INCREASES energy, altertness, focus

Can produce DEPENDENCE w/ daily use

Mode of action:
- inhibits enzyme that breaks down cyclic adenosine monophosphate
- increase in cAMP leads to increase in glucose production = more ENERGY/HIGHER cell activity

61
Q

What are cholinergic agonists?

Example?

Mode of action?

A

Ex) Nicotine

STIMULANT at LOW doses (increase energy, alternetness, focus)

RAPID TOLERANCE and DEPENDENCE (psychological & pysiological)

Mode of action:
- stimulates acetylcholine nicotinic receptors
- indirectly causes release of acetylcholine and several other neurotransmitters (dopamine)

62
Q

What are GABAergic agonists?

Example?

Mode of action?

A

Ex) Benzodiazepines

REDUCE anxiety, induce relaxation, some used to terminate seizures

RAPID TOLERANCE and DEPENDENCE

Mode of action:
- excitation of the GABA receptor produces influx of CL-
- hyperpolarizes membrane
- widespread reduction of neuronal firing underlies the behavioural effects of these drugs

63
Q

Dose of GABAergic agonists dramatically influence effect on behaviour…

What does a low dose do?

VS

What does a high dose do?

A

Low dose:
REDUCE ANXIETY

High dose:
SEDATION, COMA & EVEN DEATH

64
Q

What are glutamatergic antagonists?

Example?

Mode of action?

A

Ex) PCP and Ketamine

Can produce HALLUCINATIONS, OUT-OF-BODY EXPERIENCES

Ketamine can be used as anesthetic or for a treatment of depression

Mode of action:
2 types:
***- block NMDA receptor
- block AMPA receptor

***OUR EXAMPLES BLOCK NMDA RECEPTORS

65
Q

What are dopaminergic agonists?

Examples?

Mode of action?

A

Ex) Cocaine, amphetimine, methamphetamine (includes adderall & ritalin)

INCREASES energy, weight-loss, focus

Chronic recreational use associated w/ high rates of PSYCHOSIS

Mode of action:
- increases amount of dopamine in synapses to increase activity at dopamine receptors

66
Q

What is the dopamine hypothesis of schizophrenia?

A

Proposes some forms of the disease may be related to EXCESSIVE DOPAMINE activity (in frontal lobes)

Dopamine antagonists widely used since mid 1950’s
- actions of D2 ^^^ not fully understood
- long-term first generation antipsychotics can CAUSE tardive dyskinesia
- use of dopamine antagonist drugs that preferentially bind to D2 receptors has REDUCED SIDE-EFFECTS

***found it helped with side affects in terms of schizophrenia (reducing dopamine)

67
Q

What are serotonergic agonists?

Examples?

Mode of action?

A

Most of these also have adrenergic activity

Ex) Mescaline, psilocybin, LSD

HALLUCINOGENIC (can alter perception/sensation)

Mode of action:
- varies hahahahahah

68
Q

What are the 3 major catergories for depression treatment? (Serotonergic agonists)

***THINK OF WHAT YOU TAKE - CITALOPRAM - WHAT IS THAT????

A
  1. Monoamine oxidase (MAO) inhibitor:
    - blocks enzyme monoamine oxidase from degrading serotonin, norepinephrine and dopamine
  2. Tricyclic:
    - blocks serotonin reusable transporter proteins
  3. Selective serotonin repuatke inhibitor (SSRI)
    - blocks serotonin reuptake into presynaptic axon terminal
69
Q

What are opioidergic agonists?

What are the 3 sources?

A

Endogenous/exogenous compound that BINDS to opioid receptors to produce NARCOTIC and/or ANAGESIC effects

3 sources:
1. Isolated (morphine, codiene) BETTER
2. Altered (heroin, oxycodene) SLIGHTLY BAD
3. Synthetic (fentanyl, methadone) BAD

***GET BAD AS THEY GO ON…

70
Q

What are 3 important things to know about opioids?

A
  1. ALL opioids are potently ADDICTIVE (opioid crisis)
  2. Opioid INGESTION produces wide-ranging PHYSIOLOGICAL CHANGES
  3. Naloxone (narcan) acts as an ANTAGONIST at opioid receptors
    ***REMEMBER WHEN DAD TALKS ABOUT THIS
71
Q

What are cannabinergic agonists?

Example?

A

Ex) Tetrahydrocannabinol (THC) - one of 84 cannabinoids and main psychoactive constituent in cannabis

ALTERS MOOD by interacting w/ the CANNABIDIOL 1 (CB1) receptor found on neurons

Also binds w/ CB2 receptors on glial cells/body tissues

72
Q

The presynaptic membrane forms the “______ ________” and the postsynaptic membrane forms the “_________ ________”

A

Axon terminal; dendritic spine

73
Q

Chemical synapses can show what? (Compared to electrical synapses)

A

Plasticity

74
Q

In the PNS the neurotransmitter at the somatic muscles are “_________”, in the ANS, preganglionic “_____________” neurons from the spinal cord connect with postganglionic “_____________” neurons for parasympathetic activity and with postganglionic “__________” for sympathetic activity

A

Acetylcholine; cholinergric; cholinergric; noradrenergic

75
Q

What are the two small-molecule transmitters used by the enteric nervous system?

A

Serotonin and dopamine

76
Q

Unrelieved stress promotes excessive release of “________” which damages “__________” neurons

A

Cortisol; hippocampal

77
Q

The hypothalamus produces “____________,” which stimulate the “_________ _______” to secrete “__________ ________” into the circulatory system. Hormone levels circulating in the bloodstream send feedback to the “__________”

A

Neurohormones; pituitary gland; releasing hormones; brain

78
Q

Stress response fast-acting pathway is mediated by the release of “___________” and a slow-acting pathway mediated by the release of “____________”

A

Epinephrine; cortisol

79
Q

What are the key differences b/w neurotransmitters, neuromodulators, and hormones?

A

Neurotransmitters: released by PREsynaptic neurons and influence adjacent POSTsynaptic neurons

Neuromodulators: diffuse from a neuron to produce effects on receptors in an ENTIRE brain region

Hormones: released by neurons or tissue and distributed throughout the body via the CIRCULATORY system

80
Q

What is behaviour myopia?

A

People under the influence of a drug to respond to a restricted set of IMMEDIATE and PROMINENT cues while ignoring more REMOTE and POSSIBLE consequences

81
Q

What is disinhibition theory?

A

Alcohol is a severe depressant effect on the cortical brain region that controls judgement

While sparing more unlearned behaviours such as desire

Alcohol depresses LEARNED INHIBITIONS based on reasoning and judgment while releasing the “beast” within

***PSYCH 275- Brain & Behaviour (9 decks)

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