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Theme 1: Fundamental Neuroscience and the Brain > How drugs control the brain > Flashcards

How drugs control the brain Flashcards

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1
Q

GABA(A) ionotropic receptors

A

Ligand gated Cl- chanell

Fast IPSPs

Mainly GABAergic interneurons

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2
Q

GABA(B) metabotropic receptors

A

GPCR

Indirectly coupled to K+ or Ca2+ channel through 2nd messenger

Slow IPSPs

Both pre and post synaptic

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3
Q

GABA(A) receptors

A

Heteropentameric structure

2 alpha and 3 more subunits

Cl- channel gated by the binding of two agonist molecules

Cl- potential near resting potential

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4
Q

GABA(A) and drugs

A

Muscimol- direct agonist

Micuculline- direct antagonist

Benzodiazepine- indirect agonist

Barbiturtes- indirect agonist

Alcohol- indirect agonist

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5
Q

GABA(A) benzodiazepine action

A

Bind to alpha subunit

Changes conformation so receptor is more effective

  • reduce anxiety
  • cause sedation
  • reduce convulsions
  • relax muscles
  • cause amnesia
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6
Q

GABA(A) barbiturates and alcohol

A

Bind at different sites

Enhance GABA(A) activity

Combining the two can be fatal

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

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7
Q

Doses of alcohol

A

Low- mild euphoria and anxiolytic effects

Higher- incoordination, amnesia

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8
Q

GABA(B) receptor

A

Gi coupled- inhibits adenylyl cyclase

GBy increases K+ conductance, decreases Ca2+

Slow hyperpolarising current

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9
Q

GABA(B) and baclofen

A

Agonist

Used as a muscle relaxant to reduce spasticity

e.g. in Huntington’s disease

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10
Q

Neurotransmitter system

A

Glutamate and GABA are main workhorse of the brain

Glutamate neurones- primary route of sensory and motor information and relay neurones between brain areas

GABA neurones- interneurones, maintain balance between excitation and inhibition

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11
Q

The diffuse modulatory systems

A

Modulate activity of glutamate and GABA

  • dopaminergic
  • serotonergic
  • noradrenergic
  • adrenergic
  • cholinergic
  • histaminergic
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12
Q

Patterns of communication in the NS

A

Point to point systems

Hormones released by the hypothalamus

ANS neurones activating body tissues

Diffuse modulatory system with divergent axonal projections

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13
Q

Dopamine neurones

A

Cell bodies in the midbrain

Project into the forebrain

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14
Q

The dopaminergic system

A

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

Mesolimbic system

Mesocortical system (behavioural effects)

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15
Q

Dopamine receptors

A

Metabotropic receptors

D1 (1-5)

  • Gs
  • stimulate adenylyl cyclase
  • stimulate phospholipase C postsynaptic

Gi

  • inhibit adenylyl cyclase
  • open K+ channels
  • close Ca2+ channels postsynaptic
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16
Q

Nigrostriatal system

A

Cell bodies in the substantia nigra project to the striatum

Important part of the basal ganglia involved in movement

17
Q

Dysfunction of nigrostriatal pathways

A

Parkinson’s disease
- destruction of DA projections from SN to basal ganglia

Huntington’s disease
- destruction of DA target neurons in striatum

18
Q

Drugs for dysfunction of nigrostriatal

A

L-DOPA

MAOi

DA receptor agonists

19
Q

Mesolimbic system

A

Cell bodies in VTA project to NAcc in limbic system

Role in reinforcement (reward) of several categories of stimuli

20
Q

Dysfunction of mesolimbic system

A

Addiction

Most drugs of abuse lead to enhanced DA release in the NAcc

e.g. cocaine and amphetamines

21
Q

Mesocortical system

A

VTA projections to prefrontal cortex

Role in functions such as working memory and planning

22
Q

Dysfunction in mesocortical system

A

Schizophrenia

23
Q

Typical antipsychotics

A

Chlorpromazine and haloperidol

DA receptor antagonists

Increase DA turnover

Blockade of postsynaptic systems

24
Q

Atypical antipsychotics

A

Clozapine (D4)

Specific to receptor subtype

25
Q

Serotonergic system

A

Nine raphe nuclei in reticular formation with diffuse projections

Descending projections to cerebellum and spinal cord

Ascending reticular activation system

Dorsal and media raphe project throughout the cerebral cortex

26
Q

Function of serotonergic system

A

Mood

Sleep

Pain

Emotion

Appetite

27
Q

Selective serotonin reuptake inhibitors

A

Fluoxetine (Prozac)

Increases serotonin function by preventing its uptake

Treatment for depression and anxiety disorders

28
Q

MDMA

A

Causes serotonin transporters to run un reverse

Increased release of serotonin and blocked reuptake

29
Q

LSD

A

Hallucinogen

Causes dreamlike state with altered sensory perceptions

LSD potent agonist at 5HT1A receptor

30
Q

The noradrenergic system

A

Projections from the locus coeruleus throughout the brain

Role in arousal and attention

Metabotropic receptors

  • alpha1 Gq
  • alpha2 Gi
  • beta 1,2,3 Gs
31
Q

The adrenergic system

A

Primarily in lateral tegmental area, projecting to thalamus and hypothalamus

Acts on alpha and beta adrenergic receptors

32
Q

The cholinergic system

A

In the periphery

ACh at NMJ and synapses in the autonomic ganglia

In the basal forebrain complex
- cholinergic innervation of hippocampus and the neocortex

In the brain stem complex

  • innervates the dorsal thalamus and telencephalon
  • control excitability of sensory relay neurones
33
Q

Myasthenia gravis

A

Autoimmune disease

Destroys cholinergic receptors in the muscle

Muscle weakness and eventual loss of muscle activity

34
Q

Alzheimer’s disease

A

Loss of cholinergic neurons in the basal ganglia

Possibly underlies deficits in memory associated with disease

35
Q

Epilepsy

A

Autosomal dominant nocturnal frontal lobe epilepsy

Associated with mutations in nicotinic receptor genes

36
Q

Acetylcholinesterase inhibitors

A

Prolong action of acetylcholine at the synapse

  • treat alzheimers (physostigmine)
  • treat myasthenia gravis ( neostigmine)
37
Q

Muscarinic receptors

A

M1,3,5

  • via Gq to phospatidylinositol hydrolysis
  • smooth muscle glands

M2,4

  • via Gi to inhibit cAMP
  • smooth and cardiac muscle
38
Q

Nicotinic receptors- ionotropic

A

5 subunits surrounding central pore

Muscle and neuronal receptors different

39
Q

Histaminergic system

A

Arousal and attention

Reactivity of vestibular system

Mediation of allergic responses

Influence of brain blood flow

3 GPCRs

Theme 1: Fundamental Neuroscience and the Brain (20 decks)

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