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Drugs that affect the NS > Week 1-6 > Flashcards

Week 1-6 Flashcards

1
Q

Describe the PNS and what NTs are used in it.

A

single fibre, unattached to SC

ACh and muscarinic receptors

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2
Q

Describe the SNS and what NT’s and receptors are in it.

A

multiple fibres, attached to SC

NA, ACh

alpha and beta adrenoceptors, N-receptors

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3
Q

PNS and SNS do not have action on …?

A

S - bronchi

P-BV’s

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4
Q

Describe NA synthesis

A
  1. Tyr diffuses into cell
  2. Tyr hydroxlase converts it –> L-DOPA
  3. Dopa decarboxylase converts L-DOPA–> DA
  4. DA is precursor to NA (converted once in vesicle)
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5
Q

What happens when a-methylDOPA is in the neuron?

A

it is a competitive inhibitor of DOPA decarboxylase

it is converted –> a-methylNA which is an a2-agonist

decreases BP but exacerbates depression

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6
Q

What does 6-hydroxydopamine do in the NA synthesis pathway?

A

forms a toxic metabolite, very reactive oxidative agent –> damage

kills NAergic and DAergic nerve terminals (neurodegeneration)

destroys vesicles

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7
Q

Sympathomimietics, Tyramine and amphetamine force release of NA vesicles, describe the process.

A
  1. affinity for neuronal uptake but not MAO
  2. higher affinity for vesicular uptake, cross membrane
  3. displace NA from vesicle (may burst or release)
  4. NA into neuroeffector junction
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8
Q

describe selective transmitter depletion by Reserpine.

A
  • interferes with vesicular transport, no DA uptake therefore no NA synthesis
  • stores decrease
  • exocytosis still occurs, no NA release
  • 24-48hrs
  • decreases BP, can cause depression
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9
Q

describe guanethidine, the adrenergic neuron blocker.

A
  • selectively accumulates in neuron
  • prevents exocytosis by blocking Ca2+ entry
  • some displacement of NA from vesicles
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10
Q

What is co-transmission and what expeiment is done to show it?

A

two vesicle populations = co-transmission

experiments with reserpine show ATP is also a NT

Reserpine pererentially depletes NA stores, but ATP still signals

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11
Q

what is the primary inactivation mechanism for NA?

What are the other mechanisms?

A

neuronal uptake = pimary, inhibition increases NA in junction rapidly

metabolism = secondary, MAO breaks down NA, blocking MAO = slow increase

NA can also regulate own release, i.e. activate receptors on own terminal that inhibit release

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12
Q

what is clonidine?

A

inhibits sympathetic neurotransmission (pre-synpatic autoinhibition)

a2-adrenoceptor partial agonist

opertates when: lots of NT release, NT accumulated in high concentrations

auto-receptors: act by NT that comes out of nerve terminal

hetero-receptors: act by other NT that regulates NT release

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13
Q

different adrenoceptors are coupled to different IC GP’s?

A1 ?

B?

A2?

A

A1 = IP3/DAG/Ca2+

B = increase cAMP

A2 = decrease cAMP

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14
Q

which other factors is ACh taken into vesicle with?

A

ATP and VIP

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15
Q

What proteins help trap and transport vesicles to terminal and allow NT release

A

SNARE proteins

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16
Q

How is ACh inactivated in the synapse?

A

by metabolism

ACh esterase breaks down –> choline + acetic acid

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17
Q

Which drugs target ACh esterase’s?

A

Alzheimer’s disease drugs, cholinesterase inhibitors

irreversible inhibitors (anticholinesterases)–> death

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18
Q

what are cholinergic pathways associated with?

A

arousal, learning and memory, motor control, dependence

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19
Q

A. muscaria effects which receptors?

A

muscarinic receptor (cholinergic)

GPCRs, in PNS, slow response

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20
Q

What type of receptors are Nicotinic receptors?

A

fast response, AP propagation

in skeletal muscle and SNS

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21
Q

describe action of slow NT’s

A

GPCR’s, subunit modulation of ionchannel/enzyme

set threshold levels, not inhibit/activat AP

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22
Q

why are NT’s called neuromodulators?

what is neuromodulation?

A

because neurons recieve and integrate before transmitting

it is a post-synaptic action

neuromodulation = regulation of neuronal excitability (ion channels, IP3/DAG Ca2+)

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23
Q

what action does NPY have co-transmitting with NA?

A

it enhances the action of NA

(same as VIP and ACh)

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24
Q

describe the co-transmission of ATP with NA.

A

ATP works through GPCRs and ligand-gated ion channels

therefore fast AP with ATP and slow AP with NA

slow NT often coupled with a fast NT

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25
Q

what factors modulate the presynaptic output?

A
  • duration of opening: more/less AP - controls Ca2+ release
  • receptor reg: regulate key ions involved in exocytosis
    • Gi –> less PKA –> K- and Ca2+ –> less NT release
  • key to relase is Ca2+
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26
Q

what are receptor mediated control of cellular mechanisms?

A

ion channel-dependent: kinetics, voltage-dep

ion channel independent: protein phosphorylation, IC Ca2+ store

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27
Q

decribe in general characteristics of NTs in the CNS.

A
  • must cross BBB
  • more than 1 NT for disorders: depress (=DA, NA, 5HT)
  • 1 NT involved in many pathways
  • receptor subtypes - pot for selectivity
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28
Q

What is denervation supersensitivity?

A

sensitivity of organs to exogenously applied NT increases after nerve terminals are destroyed

ACh normally doesnt reach most post-synaptic receptors (ACh esterase, tight junctions etc). Denervation –> more R’s freely available; effect is exaggerated

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29
Q

What are some NA-channel drugs?

A
  • DTT - facilitate opening, inhibit inact
  • TTX - blocks selectivity filter with high affinity
  • local anaesthetics - bind inner pore
  • some are use-dependent (only when channel is active)
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30
Q

describe the activation and action of Kir channels

A
  1. lig activation of GPCR
  2. beta and gamma sub’s bind Kir to activate
  3. K+ flow into cell (repolarise)
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31
Q

describe action of KATP channel.

A
  • SUR = reg. domain on KATP
  • channel opens when ATP levels fall
  • smooth muscle relaxants work by opening channel
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32
Q

how does the KATP channel work in high blood glucose to release insulin?

A
  1. causes inhibition of KATP
  2. depolarise pancreatic islets cells
  3. ↑ IC Ca2+
  4. release insulin
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33
Q

what is TRPV4 modulated by ?

A

phosphorylation and protein-protein interaction

is activated upon phosphorylation

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34
Q

what is TRP coupling?

A

activation of GPCRs coupled with depolarising ion channel

e.g. pain sensors

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35
Q

what are the 3 mechanisms for mechanotranduction?

A

stretch activation

tethered (cytoskeleton pulls open)

indirect gated

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36
Q

describe general aspects of NMDA channels.

A

lig-gated, non-specific cation channels

non-linear relationship between Vm and glu-induced current - outward rectification

due to Mg2+ that blocks channel in voltage-dep manner

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37
Q

what are the nicotinic ACh receptors and what outcome when activated?

A

Nm/Nn

net Na2+ influx

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38
Q

decribe general differences between iontropic and metabotropic receptors.

A

fast transmission = iono (lig-gated), generally pentameric

slow transmission = metabo, (GPCRs)

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39
Q

decribe Glu and GABA synthesis/metabolism

A
  • Glu <–>
    • glutamine (glutamine synathase)
    • GABA (glutamate decarboxylase)
    • a-ketoglutarate
  • GABA –> succinic semialdehyde

glutamine –> Glu –> GABA

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40
Q

decribe the features of the GABAA receptor

A

iontropic, 5 sub’s, a-sub is essential for forming Cl- channel

when GABA binds –> active –> hyperpolarise

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41
Q

what are the potentiates of GABAA

A

benzodiaepines - +ve allosteric modulators

  • bind gamma but is affected by a + b
  • sedative, hypnotic, muscle relaxant
  • tolerance dependence
  • increase pore opening frequencey

Barbiturates e.g. pentobarital

  • bind a-subunit
  • increase opening time
  • anti-anexity, insomnia

non-benzodiazepines e.g. stilnox

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42
Q

what is an activator of GABAA ?

A

muscimol - hyperpolarises

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43
Q

what are some inhibitors of GABAA ?

A
  • Bicuculline - decrease GABA binding
  • Picrotoxin - binds pore, no Cl- influx
  • Penicillin - open channel block

–> seizures

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44
Q

decribe the structure of GABAB and known agonists and antagonists.

A

metabotropic, heteromeric

Bacleofen: agonist

  • roles in addiction and pain

Saclofen: antagonist

*

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45
Q

describe GHB and the action on GABA(B)

A

acts on GHBR, high affinity agonist

acts at GABA(B) as partial agonist

euphoria, disinhibitions, addicition, seizures

Precursor of GABA, effects likely due to GABA synthesis

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46
Q

describe the structure and actions of GABA(C).

A

iontropic receptor (single sub)

share homology with GABA(A) but not modulated by barb’s, benzo’s etc

GABA more active at C than A

selectively activated by analogues of GABA (CACA) and blocked by TPMPA

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47
Q

what are the the GABA transports and which drugs enhance GABA transmission?

A
  • 3 subtyes
  • Gabapentin - increase release of GABA
  • Vigabatrin - irreversible inhibitor of GABA transaminase
  • Tiagabine - decrease GABA uptake by neuron (blocks GAT-1)
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48
Q

decribe the actions of Glycine as a NT.

A
  • inhibitory + excitatory NT in the SC
  • GlyR is related to GABA(A) - pentameric Cl- channel
  • Tetanux toxin - blocks Gly release
  • Gly involved in SA control od respiration
  • # Gly is co-agonists activating NMDA-Glu receptor# blocking GlyT increases Gly and cognitive enhancement
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49
Q

what is a flavinoid?

A
  • Flavinoids, potential for management of neurological and psychiatric conditions
  • possible flavinoid site on GlyT’s (transporters)
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50
Q

what is the transition of Glu in synapse?

A

astrocyte –> nerve –> junction –> astrocyte

key link between astrocyte and neuron as neuron cannot recycle Glu

astrocyte uptake Glu –> glutamine

Nerve converts glutamine –>Glut

51
Q

what are Glutamatergic pathways?

A

pain, addiction, achizophrenia, BP

52
Q

what are the two major types of GluR’s and what are they all called?

A
  • ionotropic: NMDA, kainate, AMPA
  • metabotropic: 3 groups, 8 subtypes
53
Q

describe the general properties of iGluR’s

A

pentameric

NMDA = voltage-dependent, slower response (Mg2+ block need to dissociate after depolarised)

AMPA, Kainate = fast transmission

54
Q

what are the subtypes of AMPA and kainate receptors?

A

AMPA: GluR1-GluR4, homo/hetero assembly

Kainate: GluR5-GluR7 (low affinity) + KA1 + KA2 (high affinity)

55
Q

what are the subtypes of NMDA?

A

NMDAR1-NMDAR3

56
Q

what are the modulators of NMDAR?

A
  • Agonist BS- Glu, NMDA and antagonists BS: CCP
  • Gly site
  • Zn2+ site - Mg2+ can potentiate
  • MK801: antagonist, locks Mg2+
    • PCP site adjacent
57
Q

NMDAR agonists, antagonists, blockers, gly antag’s, polyamine antag’s?

A
  • ag = Glu, NMDA
  • ant = CGS 19755
  • blockers = PCP, Ketamine, Mg2+
  • Gly ant = Kynuenate
  • Poly ant = Ifenprondil
58
Q

decribe how Mg2+ is unblocked from NMDAR

A
  1. No Glu, receptor closed, Mg2+ bound, resting MP
  2. Glu bound, brief depolarisation, receptor open, blocked by Mg2+
  3. Glu bound, long depolarisation, receptor open, relief of Mg2+

needs 2 depolarisations for Mg2+ to be released

59
Q

describe what PCP does at NMDAR.

A
  • negative allosteric modulator of NMDAR’s
  • potentially neuro-protective but at expense of anaethesia and psycosis, may disrupt necessary excitatory transmission
  • very limited safe dose
  • effects - disorientation, agitation, ataxia, euphoria
60
Q

Describe the action of ketamine on NMDAR.

A
  • non-comp NMDAR antagonist
  • binds mu and sigma opioid receptors at high concentrations
  • hypnotic, analgesic, amnesic
61
Q

what is long term potentiation and its relation to ketamine?

A
  • LTP = form of synaptic plasticity that underlies learning and memory
    • requires sustain neuronal firing
    • dependent of NMDA receptor activation
    • involves reterograde signalling (NO)
    • increase of signalling between 2 neurons = memory
  • ketamine blocks NMDA therefore is amnesic
62
Q

mGluR group I : subtypes, signal transduction mechanism

A

mGluR 1 + 5

increase PLC/IP3 –> more Ca2+

agonist: quisqualate

63
Q

mGluR group II: subtypes, signal transduction mechanism

A

mGluR 2,3

decrease AC/cAMP production –> less Ca2+

agonist: LY354740

64
Q

mGluR group III : subtypes, signal transduction mechanism

A

mGluR 4, 6, 7, 8

decrease AC/cAMP - less Ca2+

agonist : L-AP4

65
Q

excitotoxicity is caused by….?

A
  • too much Glu in synapse –> too much IC Ca2+–> apoptosis
  • Ca2+ –> PKC, NOS, PLC, CaM etc
  • excessive activation of iGluRs and group I mGluRs = neurotoxic
  • cascades of events:
    • enzymes activations
    • generation of free radicals
    • stimulation of inflammatory cascasdes
    • gene act and neuronal death
66
Q

BMAA is weakly excitotoxic, explain its role.

A
  • in cycad seeds
  • bats eat seeds, too low to be toxic
  • concentrated in bats so when humans eat –> damage
67
Q

what is the problem when blocking NMDA receptors in the event of excitotoxicity?

A

normal excitatory function is vital, will stop all synapses

high affinity =coma

moderate affinity = hallucinations (PCP) or drowsiness (K)

68
Q

Memantine is an anti-parkinson’s agent, how does it work?

A

memantine

inhibits NMDA receptor-induced current

neuroprotection by low affinity, uncompetitive, open-channel blocker of NMDA

if given before stroke –> protection (difficult to admin at right time)

69
Q

what are excitatory amino acid transporters?

A
  • EAATs have a metabolic role of Glu uptake and turning it into glutamine and pumping back into neuron
  • EAATs on astrocytes and presynaptic neuron (not in junct)
  • EAAT1,2 = glial
  • EAAT 3-5 = neuronal
70
Q

what is the clincal significance of EAATs?

A
  • not metabolism of Glu therefore EAATs can prevent excitotoxicity
  • mutations of EAATs = predisposition to schiz
  • drugs:
    • comp substrate - heteroexchange (force Glu out of cell)
    • blocker - no heteroexchange (more Glu in junc)
    • want reversal
  • glial EAAT especially important in preventing excitotox
  • EAAT modulation - GluR’s, proteins, GF receptor…
71
Q

giving a brief summary how to drugs targeting GluRs and EAATs help in excitotox?

A
  • iGluR blocker potentially beneficial but s.e. (seizures, PCP-like)
  • mGluR modulation promising - subtype selective allosteric
  • EAAT promising, blockage difficult to be selective… modulation?
72
Q

what is the RLS in DA synthesis?

A

tyrosine hydroxylase (TH)

73
Q

how is the action of DA inactivated?

A

re-uptake (DA transporter)

metabolism (MAO), major products: HVA + DOPAC

DOPAC:DA is index of dopaminergic activity

74
Q

describe the general features of D1-like receptors

A
  • GPCRs
  • D1 and D5
  • they activate Gs and increase AC activity
  • D1 localised to cortex, neostriatum
  • D5 localised to hippo and hypoth
  • distinct localisation but some overlap

agonist: SKF38393
antagonist: SCH23390

75
Q

describe the general features of D2-like receptors.

A
  • D3, D4, D2
  • activate Gi and decrease AC activity
  • D2 local to neostriatum, pitu
  • D3 local to N.accumbens
  • D4 local to midbrain, amygdala
  • D2 ag = bromocriptine
  • D3 + D2 ant = raclopride
  • D3 ag = quinpirole
  • D4 ant = clozapine

quinpirole prefers D3 but in vivo affects D2 and D4 also

76
Q

which D receptors are pre synaptic as well as post?

A

D2

77
Q

what are the cell groupd of DA neurons in the CNS?

A

nigrostriatal pathway (A9) - motor control

mesolimbic pathway - emotion, addiction (A10)

tuberoinfundibular pathway (A12) - hormone control

Hypothalamic cell groups (A11, A13) - temp control, sexual behaviour

78
Q

describe the DAergic system in the BG, direct pathway.

A
  1. D1 sends excitatory (Glu) signal to striatum OIR motor cortex sends excitatory sig
  2. Striatum inhibits Globus pallidus internal + substrantia nigria
  3. this removes tonic inhibition to thalamus
  4. excitatory signal to supplementary motor cortex
79
Q

describe the indirect DAergic pathway in BG

A
  1. D2 pathway sends inhibitory signal to striatum
  2. GPe is ihibited
  3. sub-thalamic nucleus is inhibited
  4. this activates the GPi and increases tonic inhibition to thalamus
80
Q

describe the symptoms and cause of Parkinson’s and what therapy aims to do

A
  • tremor, musclar rigidity, motor disorder
  • DA deficiency: degen of nigrostriatal system
  • therapy aim:
    • L-DOPA combined with DOPA decarboxylase inhibitor - boosts DA (inhibits peripheral metabolism)
    • muscarinic antag’s
    • DA agonists
  • new treatments - transplants, growth factors
81
Q

what NT’s are involved in treatment of depression?

A

NA, 5HT, DA

82
Q

describe the role of BDNF in depression

A

BDNF = brain-derived neurotrophic factor

helps protect neurons and can lead to neurogenesis, majorly involved in neuroplasticity

altered (decreased) levels in depressed people

83
Q

what is the biosynthesis steps of 5HT?

A

tyrophan –> –> 5HT

84
Q

5HT and NA containing cells located where in the brain?

A

5HT - raphe nuclei

NA - locus coeruleus

85
Q

what type of receptors are NA and 5HT receptors?

A

GPCRs except 5HT3 which is ligand-gated

86
Q

can drugs be selective on 5HT and NA receptors?

A

Serotonin receptors in brain with diff functions – selectively target

NA receptors - alpha and beta receptor have many subtypes - elicit diff bhevaiours

87
Q

decribe MAOi’s as treatment of depression.

A
  • inhibit oxidase A and B (non-specifically so s.e.)
  • structurally similar to MAO substrates
  • increase MA in cytoplasm
  • delayed anti-depressant effect
88
Q

describe tricyclic antidepressant (TCA) action

A
  • block re-uptake of NA, 5HT into nerve terminal
  • each drug is selcetive for one MA system over another
  • all have 3 rings
  • s.e. = sedation, antiACh, decrease BP, increase weight
89
Q

decribe selective serotonin reuptake inhibitors (SSRIs)

A
  • selective for 5HT uptake, weak inhib of NA and DA uptake
  • few adrenergic, histamine, muscarinic effects
    • no cognitive or movt s.e.
  • kinetics - oral absorption long 1/2 life
  • e.g. prozac
  • s.e. = nausea, insomnia, agitations, loss of libido
  • advantage = safer in OD
  • numerous drug interactions
90
Q

what is the “porsolt” test?

A

test to see whether drug acts on mood

rat forced to swim, no escape

drug = immobility

91
Q

what are the suggestions why anti-depressants come on slowly?

A
  • altered alpha/beta receptor levels. Sensitisaton desensitisation
  • modulation of serotonic receptor levels and signalling
  • BDNF activation? serotoneric and NAergic BDNF synthesis and BDNF levels must increase (takes time)
  • nerogenesis? increase activation of MA causes increase in neurogenesis (takes time)
92
Q

describe the role of serotonin-1A receptor in action of SSRIs

A
  • seoteronergic neurons - low activity in depression
    • low level of release
    • upreg of Rs on post and high pre Rsinhibiting action
  • give SSRI, not much action first as only few transporters and not much 5HT in cleft
  • most R’s on dendrites
  • SSRIs block 5HT uptake at dendrites and junction - increase 5HT and activate dendrite R’s
  • causes desen of 5HT1 receptors on pre- down reg
  • less inhib of cell body, so increase 5HT release
  • large up-reg of 5HT causes down-reg of post R’s
  • eventually normal amount of R’s - TAKES TIME
93
Q

describe electroconvulsive therapy.

A

electrical stimulation via electrodes on head

given anaethesia, muscle relaxant

effective in depression

94
Q

describe Li as a treatment for bi-polar disorder

A

narrow therapeutic index - must mointor levels

mechanism unclea

side effects - nausea, tremor, decrease thyroid func

95
Q

what is neuropathic pain?

A

pain generated by NS

response to analgesics is not very good

lasts indefinitely may esclate

hypersensitivity and allodynia

96
Q

describe basic pain perception

A
  • following activation of nocicptors (high threshold)
  • transmission of info –> dorsal horn
  • may be inhib/amp by descending tracts or local circuits
  • info –> high centres (thalamus)

nociceptive afferents in dorsal root ganglia

97
Q

what is the general action of opioids?

A

decrease activity of relay neurons in the synapse of dorsal horn

modulates activity at mu-opioid receptors

signal weakened at pre-synaptic end but pain-inhib neuron which inhib the relay neuron

98
Q

what happens on a molecular level with mu-opioids?

A

opioids have direct GPCR actions on neurons:

  • close-voltage gated Ca2+ channels on pre-synaptic nerve terminals - decrease NT release (excitatory NTs: glu, ACh, NA, sub P etc)
  • hyperpolarise and inhibit post-synaptic neuron by opening K+ channels
99
Q

what are the major side effects of opioids?

A

respiratory depression, miosis, euphoria, decrease GI motility, dependence, nausea and vomitying, broncho-constriction

100
Q

describe morphine pharmacokinetics and tolerance

A

significant hepatic metabolism (metabolite more potent anaglesic)

excreted in urine

1/2 lige 3-6 hours

tolerance: to anaglesia, euphoria, sedation, nausea BUT not constipation and miosis

101
Q

describe the properties of fentanyl

A

synthetic mu-agonist

100 times more potent than morphine

short 1/2 life, no active metabolites and less CNS adverse effects than morphine (crashes)

transdermal patch - well absorbed through skin - for chronic stabilised pain

102
Q

describe the properties of methadone

A
  • mu-agonist
  • orally active
  • long 1/2 life so withdrawal less intense (comes off slowly)
  • accumulation may occur because of 1/2 life
103
Q

what are some drug types for opioid-resistant patients?

A
  • N-type Ca2+ antagonists
  • pregablin
  • cannaboid agonists
  • adjuvants
104
Q

describe N-type Ca2+ antagonists in pain-relief

A

ω-conotoxin peptides

  • n-type channel = main entry route for Ca2+, critical for NT release
  • ω-conotoxin is highly selective blocker
  • admin via intrathecal catheter (major s.e. with i.v. )
105
Q

describe pregablin as an analgesic and the significance of α2δ protein

A
  • modulates hyperexcited neurons
  • readily crosses BBB
  • inactivate at GABA receptors
  • Binds α2δ subunit of N-type Ca2+ channels
  • modulates (not block) activity, to decrease NT release
  • α2δ protein is not present on all types of channels, so no BP side effects
  • α2δ enhances channel function, up-reg un damaged sensory neurons
106
Q

describe the action of cannaboid agonists in analgesia.

A
  • effects: analgesia, motor coord, CV, memory disruption, appetite stimu
  • CB1 receptors in primary sensory neurons
  • CB1 receptors in dorsal horn
    • presynaptic, associated with N-type
    • interneuronal, inhibit release of excitatory NTs
  • descending modulation - central CB1 agonism via a2-receptor
  • CB1 receptor activation inhibits NT release via Ca2+ channel entry inhibition and hyperpolarisation
107
Q

what is sativex?

A

analgesic adjuvant

active ingredients = THC + cannabidol

108
Q

why is morphine often given in combination with another analgesic?

A

can be given with cannabinoid agonist

2 at lower doses so less side effects (especially when at diff R’s)

adjuvants used as supplement and may decrease opioid s.e. by enabling lower doses

109
Q

how are NMDA antagonists used as adjuvants in analgesia?

A

they stop activation

persistent nociception may activate NMDA receptors in dorsal horn –> central sensitisation

e.g. ketamine

110
Q

how does drug-related stimuli atain salience?

A
  • euphoria is produced by over-activating “pleasure/limbic” centres in brain via release of DA in N.accumbens
  • the limbic system is tied to learning e.g. hippocampus
  • repeatedly pairing drug-induced euphoroa with drug-related stimuli creates an association
111
Q

what is cue-induced brain activation in drug addiction?

A

when showing users drug-related stimuli that activates the limbic regions associated with the effect of the drug

strength of cravings is reflected in cue-related limbic activity and amount of activity can be used to predict relapse

112
Q

What is said about someone with low availbility of D2 receptors in terms of drug addiction?

i.e. possess TaqA1 allele

A
  • often linked to addiction
  • TaqA1 mediates D2 receptor density, possession of allele decreases density –> hypodopaminergic state
  • pos and neg reinforcement associated with DA stim and drug –> salience
  • more likely to be “super sensitive” even after abstinence
  • more likely to learn from reward than punishment
  • small amount of drug = big DA release
113
Q

what is predicted about soemone with a high D2 bioavailability in drug addiction?

A
  • protective factor against dependence
  • do not possess TaqA1
  • learn better from punishment
114
Q

What does the U-shaped curve predict about individuals after DA stimulation ?

A

large druge induced increase in DA results in…

  • if low D2 - optimal stimulation
  • if high D2 - unpleasant
115
Q

Why do cocaine addicts show poorer descision making?

A

less DLPFC and anterior cingulate cortex activity

greater orbiofrontal activity

116
Q

what region of the brain is related to awareness of cravings and motivations?

A

insula cortex is critcal for awareness of cravings, smokers who suffer damage to this region are 100 times more likely to quit

Insula and ACC are the limbic sensory and motor

ACC = initation of behaviours

117
Q

what is inhibitory control?

A

when conscious internal goals take precedence over automatic process

118
Q

which regions of the brain are not functioning properly in poor cognitive control?

A

right inferior frontal gyrus

anterior cingulate cortex

119
Q

what occurs when addict goes off drug in comparison to when they stay on?

A
  • cognitive function recovery is slow
  • abstinence for 1 year shows no neuropsych improvement
  • in fact taking drug shows better cognitive performance as it “normalises” patient
    • they will continue to have better performance for 6 months
    • they have increases PFC activity
120
Q

what drugs are used to improved cognitive control in drug users and what do they do?

A

modafinil and amantadine

increase DLPFC activity and cognitive performance

121
Q

how can you predict if someone will relapse into drugs?

A

“change blindness task” slightly change one-drug related item in an image. Rate of change noticing indicate dependence. you can predict a relapse by mointoring for an increase over time

poor executive function performance and associated hypoactivity in DLPFC etc and insula accurately predict relapsers

122
Q

what are the benefits to co-transmission?

A

benefits

  • amplification of signal
  • different functions - energy source (ATP) + signal
    • different cell type targets (contraction/conduction) especially in en passant synapses)
  • multiple outcomes -
    • modulation - responsiveness (NPY enhance NA) “synergy”
    • post/pre junctional reg. i.e. NPY releae at increased freq but if not released can be used to stop release
123
Q
A

Drugs that affect the NS (3 decks)

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