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Module 202 Theme 1 > How drugs control the brain > Flashcards

How drugs control the brain Flashcards

(47 cards)

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1
Q

Where is GABA mainly used?

A

Inhibitory interneurons - keep the excitation in check

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2
Q

Which neurotransmitter uses glutamine?

A

Projection neurons

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3
Q

Which neurotransmitter controls local interneurons?

A

GABA

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4
Q

Describe the GABA(A) ionotropic receptor

A

Ligand gated Cl- channel
Fast IPSPs
Mainly GABAergic interneurons
Heteropentameric structure 2 alpha and 3 more subunits
CL- channel gated by the binding of two agonist molecules. Cl - potential is near resting potential increasing chloride permeability hyperpolarizing the neuron decreasing the depolarizing effects of the excitatory input

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5
Q

Describe GABA(B) metabotropic receptors

A

G protein coupled receptors
Indirectly coupled to K+ and Ca2+ channel through 2nd messengers
Slow IPSPs
Both pre and postsynaptic

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6
Q

Name a direct agonist of the GABA(A) receptor

A

Muscimol

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7
Q

Name a direct antagonist of GABA(A) receptor

A

Bicuculline

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8
Q

Name an indirect agonist of GABA(A) receptor

A

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

Barbiturates increase the duration of channel openings (anaesthesia)

Alcohol

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9
Q

Describe how benzodiazepines work

A

Benzodiazepine binding site on the a subunit of GABA(A) receptor
benzodiazepine binds to a subunit, changes conformation of the receptor so GABA activation of receptor is more effective.

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10
Q

What are the effects of benzodiazepine

A 
Effects to: 
reduce anxiety
cause sedation
reduce convulsions
relax muscles
cause amnesia
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11
Q

Describe the action of alcohol and barbiturates on the GABA(A) channel

A

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

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12
Q

Name an agonist of a GABA(B) channel

A

Baclofen

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13
Q

Describe how the GABA(B) receptor works

A

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

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14
Q

What is the main function of glutamate neurons?

A

primary route of sensory and motor information and relay neurons between brain areas

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15
Q

What is the main function of GABA neurons?

A

interneurons, maintain balance between excitation and inhibition

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16
Q

List some patterns of communication in the nervous system

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)

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17
Q

Where are the dopamine neurons?

A

Cell bodies in the midbrain and project into the forebrain

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18
Q

What does the nigrostriatal system do?

A

75% of brain dopamine
Motor control
Cell bodies in the substantia nigra project to the striatu, (caudate nucelus and putamen) Importnat part of basal ganglia involved in movement.

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19
Q

What does the mesocortical system do?

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A

Responds to addictions and the environment
VTA projections to prefrontal cortex

Role in functions such as working memory and planning.

20
Q

Describe the D1 like receptor (1 and 5)

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A

Gs - stimulate adenylyl cyclase
- stimulate phospholipase C
postsynaptic

21
Q

Describe the D2 like receptor (2,3,4)

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A 
Gi  	- inhibit adenylyl cyclase
				- open K+ channels
				- close Ca2+ channels
			postsynaptic
			presynaptic autoreceptors (D3)
22
Q

What maintains the balance of dopamine concentration?

Study These Flashcards
A

Balance of D1 and D2

23
Q

Describe dysfunction of the nigrostriatal system

Study These Flashcards
A

Parkinsons disease - destruction of DA projections from SN to basal ganglia
Huntington’s disease - destruction of DA target neurons in striatum

24
Q

What drugs are used in the treatment of parkinsons?

Study These Flashcards
A

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

25
What is the mesolimbic system?
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
26
Describe the dysfunction of the mesolimbic system
Addiction - most drugs of abuse lead to enhanced DA release in the NAcc
27
Name some drugs that affect the mesolimbic system
e.g. 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
28
Describe dysfunction of the mesocortical system
Scizophrenia
29
Name some drugs affecting the mesocortical system
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
30
Describe the serotonergic system
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
31
List the functions of the serotonergic system
mood sleep pain emotion appetite
32
Name a selective serotonin reuptake inhibitor SSRI
Fluoxetine (PROZAC)
33
Describe how selective serotonin reuptake inhibitors work
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. synthesizing new receptors and changing pathways and cascades in the cell
34
How does MDMA (ecstasy) affect the serotonergic system?
``` causes serotonin (and norepinephrine) transporters to run in reverse increased release of serotonin and blocked reuptake ```
35
Describe how LSD affects the serotonergic system affects the serotonergic system?
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
36
Describe the noradrenergic system
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
37
Describe the adrenergic system
Primarily in lateral tegmental area, projecting to thalamus and hypothalamus. Acts on a- and β- adrenergic receptors
38
Describe the cholinerggic system
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
39
List some disorders of the cholinergic system
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
40
How do acetylcholinesterase inhibitors work?
Prolong action of acetylcholine at the synapse - Treatment for Alzheimer’s disease (e.g. physostigmine) - Treatment for Myasthenia gravis (neostigmine)
41
How does botox work?
Prevents release of ACh at the NMJ
42
How does latrotoxin work?
Permanent release - depletes ACh at NMJ
43
Name the two types of acetylcholine receptor
Muscarinic - metabotropic | Nicotinic - ionotropic
44
What is the agonist of the muscarinic receptor?
Muscarine
45
What is the antagonist of the muscarinic receptor?
Atropine
46
Describe the action of muscarinic receptors - metabotropic
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
47
Describe the histaminergic system
Arousal & attention Reactivity of vestibular system Mediation of allergic responses Influence of brain blood flow 3 G-protein-coupled Rs

Module 202 Theme 1 (28 decks)

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