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Foundations in Neuroscience > Receptors, Neurotransmitters and Drugs > Flashcards

Receptors, Neurotransmitters and Drugs Flashcards

1
Q

What is the two state model of receptor activation?

A

Receptors can exist in two states - resting or activated

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2
Q

What is the mode of action of a reversible antagonist?

A

Competes with the agonist to bind at the same site

Decreases agonist potency

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3
Q

What is the mode of action of an irreversible antagonist?

A

Binds irreversibly to receptor - may cause conformational change or reduce agonist binding ability
Decreases agonist efficacy

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4
Q

What is an allosteric modulator?

A

Substance that impacts receptor function by binding to a site distinct from the endogenous ligand
Can be positive or negative

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5
Q

What does an affinity modulator do?

A

Increase binding at receptor but do not increase level of response

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6
Q

What does an efficacy modulator do?

A

Doesn’t affect binding but increases efficacy/activity of receptor

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7
Q

Define neurotransmitter

A

Biochemical that mediates fast-acting direct communication between two neurons

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8
Q

Define neuromodulator

A

Biochemical that modulates activity of neurons/networks by changing the ability of neurons to respond to neurotransmitters
Can act at sites remote from where they were synthesised

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9
Q

Name 4 amino acid neurotransmitters and whether they are inhibitory or excitatory

A

Glutamate +
GABA -
Aspartate +
Glycine +/-

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10
Q

Name 4 biogenic amine neurotransmitters and whether they are inhibitory or excitatory

A 
Acetylcholine
Seratonin
Noradrenaline
Adrenaline
Dopamine
Histamine
Either +/- depending on receptor activated
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11
Q

How does Nitric Oxide modulate neurotransmission?

A
  1. Ca2+ influx activates nNOS
  2. Increases intracellular NO levels
  3. Activates cGMP and MAPK signalling which modulates function of postsynaptic neuron
  4. Can diffuse retrogradely and impact neurotransmitter release from presynaptic neuron
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12
Q

Give 3 examples of gliotransmitters

A

ATP, D-Serine, Adenosine, Glutamate, eicosanoids, cytokines, neuropeptides

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13
Q

How are NMDA receptors allosterically modulated?

A

By Glycine
Potentiates effect of Glutamate
Also has voltage dependant Mg2+ block

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14
Q

What are the three mechanisms of receptor desensitisation?

A

Uncoupling of agonist binding from signalling
Receptor internalisation
Reduced receptor expression

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15
Q

Define tachyphylaxis, tolerance and addiction

A

Tachyphylaxis - acute, sudden decrease in drug response
Tolerance - reduced response after chronic use
Addiction - behavioural manifestation of tolerance

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16
Q

How does acute alcohol modulate glutamatergic neurotransmission?

A

Non-competitive antagonist/negative allosteric modulator of NDMA and AMPA
Reduces glutamate release
Increases mGluR2/3 activity (reduces neuronal excitability)

17
Q

Describe the main features of the NMDA receptor

A

Cation channel - Na+ and Ca2+
Opening leads to depolarisation
Activation requires glutamate and co-agonist (glycine/D-Serine)
Voltage sensitive Mg2+ block

18
Q

How does alcohol affect NMDA receptors? How could this be investigated?

A

Acute ethanol inhibits NDMA currents
Investigate using voltage clamp experiments
Different subunits - different sensitivities
Doesn’t modulate Mg2+ block

19
Q

How does chronic alcohol intake lead to adaptations in glutamatergic transmission?

A

Increased NDMA/AMPA receptors on postsynaptic membrane
Increased ion channel conductance
Reduced glial recycling of glutamate
Desensitisation/downregulation of presynaptic mGluR - leads to increased glutamate release

20
Q

How does alcohol consumption during pregnancy affect the fetus?

A

Fetal alcohol syndrome
Impairs glutamatergic signalling in developing brain
Reduced NDMA receptors in offspring
Results in developmental/cognitive impairments

21
Q

How does acute alcohol modulate GABAergic neurotransmission?

A

Positive allosteric modulator - enhances Cl- influx through GABAa receptors
Enhanced GABA release - acting via presynaptic GABAb receptors (metabotropic)
Works differently in VTA

22
Q

Describe the main features of the GABAa receptor

A

Anion channel - Cl-
Activation leads to hyperpolarisation
Made of 5 subunits
Found synaptically (short-term inhibition) and extrasynaptically (tonic inhibition)

23
Q

How does acute alcohol affect neurosteroids?

A

Increases neurosteroid release

24
Q

How does chronic alcohol exposure lead to changes in GABAa receptors?

A

Changes in GABAa subunit composition
Reduced sensitivity of GABAa to alcohol/neurosteroids
Change in localisation
No change in receptor number
Withdrawal - rapid reversion of subunit changes

25
Q

What symptoms are present during alcohol withdrawal and why?

A

Seizures/tremors

Hyperexcitability of neurons due to loss of inhibitory tone

26
Q

How does acute alcohol affect opioids?

A

Increases opioid synthesis and release

27
Q

Define opioids and opiates

A

Opioids - chemicals that act on opioid receptors, can be endogenous or exogenous
Opiates - naturally occurring biochemicals that modulate opioid receptors e.g. morphine, heroin

28
Q

What type of signalling do opioid receptors use?

A

Act via GPCRs

29
Q

Define reinforcement

A

Strengthening the probability of future behaviour.

Mediated by the mesolimbic dopamine reward system

30
Q

How do opioids contribute to the reinforcing effects of alcohol?

A
  1. Alcohol increases brain opioid action on GABA neurons in VTA
  2. Opioids are neuromodulatory - decrease the activity of VTA GABA interneurons
  3. Cause disinhibition of VTA dopamine neurons - increased nucleus accumbens dopamine release = reward/euphoria
  4. May also act indirectly on nucleus accumbens to increase reinforcement
  5. Inhibiting opioid receptors (naltrexone) is used to aid alcohol withdrawal
31
Q

How does alcohol impact glial cell function?

A

Regulates astrocyte expression
Increased expression of amino acid transporters (GLAST and GLT-1)
Inhibiting GLAST and GLT-1 reduces rewarding/reinforcing properties of alcohol

32
Q

How do neurosteroids affect GABAa receptors?

A

Positive allosteric modulator of GABAa

Foundations in Neuroscience (6 decks)

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