Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

202 retake: theme 1 > L13 How Drugs Control the Brain > Flashcards

L13 How Drugs Control the Brain Flashcards

1
Q

describe and state the Two main families of GABA receptor:

A

1) GABA(A) ionotropic receptors

Ligand gated Cl- channel

Fast IPSPs
       Mainly GABAergic interneurons

2) GABA(B) metabotropic receptors

	G protein coupled receptors
	Indirectly coupled to K+ or Ca2+ channel through 2nd messengers
	(opens K+ channel, closes Ca2+ channel)
	Slow IPSPs
	Both pre- and post- synaptic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

describe the structure of GABA (A) receptors

A

-Heteropentameric structure - 2 a + 3 more subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

describe what occurs when a GABA(A) receptor is activated

A
  • Cl- channel gated by the binding
    of two agonist molecules
                     Cl- potential is near resting potential 
                 increasing chloride permeability 					       hyperpolarizes the neuron 		
                 decreasing the depolarizing effects of 
                 an excitatory input
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

where do indirect and direct antagonists bind to a GABA receptor

A
  • bind at GABA binding site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

state and describe a direct agonist

A

Muscimol – agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

state and describe a direct antagonist

A

Bicuculline – antagonist (experimental tool)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

state and describe an indirect agonist

A

Benzodiazepine - binding increases the receptor affinity for GABA - increase frequency of channel opening
- anxiolytic and hypnotic drugs with rapid onset, but less satisfactory in the long term

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

state and describe an indirect agonist

A

Barbiturates increase the duration of channel openings (anaesthesia, epilepsy treatment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

state and describe an indirect agonist

A

Alcohol - agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

go into more detail about the actions of a benzodiazepine on GABA (A) and give an example

A
  • diazepam (Valium)
  • Benzodiazepine binding site on the a subunit of GABA(A) receptor

Indirect agonist - benzodiazepine binds to a subunit, changes conformation of the receptor so GABA activation of receptor is more effective.

Effects of benzodiazepine are to:

  • reduce anxiety
  • cause sedation
  • reduce convulsions
  • relax muscles
  • cause amnesia

Inverse agonists bind to benzodiazepine site and have opposite effects

– produce anxiety and predisposition to convulsions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

describe in more detail the pharmacology of barbiturates and alcohol on GABA(A)

A

Bind at different sites on the receptor

Both have same effect: to enhance GABA(A) activity and effects are additive - combining the two can be fatal

Alcohol also interacts with NMDA, glycine, nicotinic and serotonin receptors.

Low doses of alcohol - mild euphoria and anxiolytic effects Higher doses - incoordination, amnesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

name and describe an agonist for a GABA(B) receptor

A

Agonist - Baclofen (used as a muscle relaxant to reduce spasticity e.g. in Huntington’s disease)

Gi coupled - inhibits adenylyl cyclase
Gbg gated K+ channels
increases K+ conductance
decreases Ca2+ conductance (presynaptically)
Slow hyperpolarizing current (late inhibitory postsynaptic potential)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

does inhibition of a GABA(B) transmission have the same effect as on a GABA(A) transmission

A

NO- Inhibition of GABA(B) transmission does not have same behavioural outcome as inhibition of GABA(A) receptors (e.g. seizure)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

name some diffuse modulatory systems

A 
Dopaminergic (DA)
Serotonergic (5-HT)
Noradrenergic (NA/NE) 
Adrenergic
Cholinergic (ACh)
Histaminergic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is a diffuse modulatory system

A

-Specific populations of neurons that project diffusely and modulate the activity of Glutamate and GABA neurons in their target areas.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the patterns of communication in the NS

A
  • Point-to-point systems
  • Hormones released by the hypothalamus
  • ANS neurons activating body tissues
  • Diffuse modulatory system with divergent axonal projections (not classical synapse)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

where are dopamine neurons found

A

cell bodies in the midbrain

project into the forebrain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what systems are included in the dopaminergic system

A
  • Nigrostriatal system (75% of brain DA)
    (motor control)

Mesolimbic system

Mesocortical system
(behavioural effects)

Tuberohypophyseal system (endocrine control)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

describe metabotropic receptors D(1-5)

A

Dopamine (DA) receptors

Dopamine produces both EPSPs and IPSPs depending on the receptor subtype and coupled G proteins

D1-like (1 & 5) Gs - stimulate adenylyl cyclase
- stimulate phospholipase C
postsynaptic

D2-like (2, 3 & 4) 	Gi  	- inhibit adenylyl cyclase
				- open K+ channels
				- close Ca2+ channels
			postsynaptic
			presynaptic autoreceptors (D3)

Balance of these systems
maintains dopaminergic
tone

20
Q

describe the Nigrostriatal system

A
  • cell bodies in the substantia nigra project to the striatum (caudate nucleus and putamen)
    Important part of the basal ganglia involved in movement.
21
Q

describe some dysfunctions associated with the nigrostriatal system

A

Dysfunction:
Parkinson’s disease
destruction of DA projections from SN to basal ganglia
Huntington’s disease
destruction of DA target neurons in striatum

22
Q

what are some drugs that help with dysfunction in the Nigrostriatal system

A

Drugs:

L-DOPA, Monoamine oxidase (MAO) inhibitors, Dopamine receptor agonists -treatments for Parkinson’s Disease

23
Q

describe the mesolimbic system

A

– cell bodies in ventral tegmental area (VTA) project to the limbic system, nucleus accumbens (NAcc)

Role in reinforcement (reward) of several categories of stimuli, including drugs of abuse

24
Q

describe some dysfunctions associated with the mesolimbic system

A

Dysfunction:

Addiction - most drugs of abuse lead to enhanced DA release in the NAcc

25
Q

describe the drugs and their short and long term effects that stimulate the mesolimbic system

A

Cocaine and Amphetamine -
psychomotor stimulants

Immediate effects:

  • give the feeling of increased alertness and self confidence, a sense of exhilaration and euphoria and a decreased appetite.
  • large doses can cause stereotypy and psychosis
  • cause peripheral effects that mimic activation of the sympathetic division of the ANS, increased heart rate and blood pressure, dilation of pupils etc.

Long-term effects:

  • natural rewards, e.g. water, food, sex increase DA transmission and leads to reinforcement of associated behaviours
  • increased DA by cocaine etc. short circuits pathway, drug taking behaviours become reinforced
  • downregulation of endogenous DA system - craving
26
Q

describe the Mesocortical system and its role

A

Mesocortical system – VTA projections to prefrontal cortex

Role in functions such as working memory and planning.

27
Q

describe the dysfunction in the Mesocortical system and some drugs used to treat them

A

Dysfunction:
Schizophrenia

Drugs:
Typical antipsychotics (e.g. chlorpromazine and haloperidol)
- DA receptors antagonists (pre and postsynaptic)
- Increase DA turnover - lose autoreceptor inhibiton
- Blockade of postsynaptic receptors - upregulation

Antipsychotic effects - action in mesocortical system

Side effects - action on other dopaminergic systems

Extrapyramidal side effects (EPS) - tardive dyskinesia etc.
(chronic blockade causes system to become supersensitive)

Atypical antipsychotics (e.g. clozapine)

- specific to receptor subtype  
	e. g. Clozapine - antagonist of D4 receptors (cortex only)

Reduce psychosis associated with schizophrenia

Antipsychotic effects without EPS

28
Q

describe the serotonergic system

A

Nine raphe nuclei in reticular formation with diffuse projections
-each projects to a different part of the brain

Descending projections to cerebellum and spinal cord (pain)
Ascending reticular activating system (with LC)

Dorsal and medial raphe
project throughout the cerebral cortex

raphe neurons fire tonically
during wakefulness

quiet during sleep

29
Q

what dos the serotonergic system function in

A

mood

sleep

pain

emotion

appetite
30
Q

describe the metabotropic serotonin receptors

A

Ionotropic

5-HT3 opens channel that fluxes Na+, K+, Ca2+ (excitatory)

Metabotropic

5-HT1A Gi raphe, hippocampus

5-HT7 Gs thalamus, hypothalamus, amygdala

5-HT2A, B and C Gq cortex, hippocampus

31
Q

describe the drugs that have an effect on the serotonergic system

A

1)Selective Serotonin Reuptake Inhibitors e.g.fluoxetine (Prozac)

increase serotonin function by preventing its uptake

treatment for depression and anxiety disorders

but depression not a simple case of low serotonergic tone
(effects not seen for 2-3 weeks)
increased availability of serotonin triggering downstream pathways
- long term modulatory effects
- second messenger cascades, gene transcription etc.

2)Methylenedioxymethamphetamine (MDMA) - ecstasy

causes serotonin (and norepinephrine) transporters to run in reverse
	increased release of serotonin and blocked reuptake
32
Q

describe LSD

A

LSD – (Lysergic acid diethylamide) hallucinogen
Causes a dreamlike state with altered sensory perceptions

LSD potent agonist at 5HT1A receptors in raphe nucleus

Hallucinogenic properties at 5HT2A receptors in prefrontal cortex

33
Q

describe the noradrenergic system

A

Projections form the Locus Coeruleus throughout the brain

Role in arousal and attention

Metabotropic receptors

Alpha adrenergic receptors
a1 Gq
a2 Gi

Beta adrenergic receptors
b1, 2 and 3 Gs

34
Q

describe the adrenergic system

A

-Primarily in lateral tegmental
area, projecting to thalamus
and hypothalamus.

Acts on a- and β- adrenergic
receptors

35
Q

describe the cholinergic system

A

In the periphery
Acetylcholine at NMJ and
synapses in the autonomic ganglia

In the brain
Basal forebrain complex
Cholinergic innervation of the
Hippocampus and the neocortex

Brain stem complex
innervates the dorsal thalamus and telencephalon
-control excitability of sensory relay neurons and provide a cholinergic link between the brain stem and basal forebrain complex

36
Q

look at slide 30 for ACh and NA in the PNS

A

how was it

37
Q

describe some Disorders of the cholinergic system

A

Peripheral-
Myasthenia gravis-
Autoimmune disease - destroys cholinergic receptors in the muscle - muscle weakness and eventual loss of muscle activity

Brain-
Alzheimer’s disease-
Loss of cholinergic neurons in the basal ganglia - possibly underlies deficits in memory associated with the disease.

Addiction: nicotine addiction

Epilepsy-
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) associated with mutations in nicotinic receptor genes.

Other psychiatric- disorders
Comorbidity with smoking

38
Q

describe the importance of AChesterase inhibitors

A

-Prolong action of acetylcholine at the synapse

  • Treatment for Alzheimer’s disease (e.g. physostigmine)
  • Treatment for Myasthenia gravis (neostigmine)

Insecticides & Chemical warfare agents, e.g. “Sarin”

Botox - prevents release of ACh at NMJ

Latrotoxin - permanent release - depletes ACh at NMJ

39
Q

what are the 2 types of ACh receptor

A

Two types of acetylcholine receptor

Muscarinic - metabotropic

Nicotinic – ionotropic

Visceral motor system / sympathetic & parasympathetic preganglionic neurons

40
Q

what is a muscarine

A

Muscarine (agonist of Muscarinic receptors – metabotropic

) found in poisonous mushroom Amanita muscaria

41
Q

what is a atropine

A

Atropine (antagonist of Muscarinic receptors – metabotropic

) belladonna alkaloid extracted from deadly nightshade

42
Q

describe some common muscarinic receptors and overall effects on neuron & whether on just post or presynaptic

A

M1
M3 via Gq to phospatidylinositol hydrolysis
M5 (smooth muscles and glands)

M2
M4 via Gi to inhibit cAMP (smooth and cardiac muscle)

Lead to opening or closing of K+, Ca2+ or Cl- channels
hyperpolarization or depolarization (cell type/receptor type dependent)

Pre and postsynaptic receptors
Presynaptic autoreceptors - negative feedback - stop ACh release

43
Q

describe muscle nicotinic receptor (structure, function, location, antagonist)

A

-2x a1, b, d and g subunits
(neuromuscular junction NMJ)
(Antagonist - curare (poison darts) - instant paralysis)

44
Q

describe neuronal Muscle receptor (structure, and location)

A

Heteromeric combination of a3,4,5 and b2,3,4 or 6
Homomeric receptors a7, 8 or 9

a3b4 on autonomic ganglia
a4b2 and a7 most common brain receptors

Vary in their pharmacology, selectivity and kinetics and conductance

Located pre and postsynaptically
Presynaptic receptors - facilitate transmitter release
(Na+ and Ca2+, depolarization and direct transmitter release)

45
Q

describe the histaminergic system

A

Arousal & attention

Reactivity of vestibular system

Mediation of allergic responses

Influence of brain blood flow

3 G-protein-coupled Rs

202 retake: theme 1 (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions