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Molecular Neuroscience III > Final Review > Flashcards

Final Review Flashcards

1
Q

The chances to develop drug addiction are highest for what drug that we studied?

A

Tobacco (highest)

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2
Q

Chronic opioid use facilitates the release of what neurotransmitter?

A

GABA

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3
Q

What is the strongest opioid?

A

Enkephalins? (met and leu?)

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4
Q

Which receptor agonist, dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion and cocaine-enhanced accumbens extracellular dopamine in wild-type

A

CB2 agonist

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5
Q

Which substances mediate sphingolipid metabolism? How?

A

Cannabinoids modulate sphingolipid metabolising pathways by:

  • Inducing sphingomyelin (SM) breakdown
  • Increasing the levels of the second messenger ceramide.
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6
Q

What prevents obesity in mice? (5)

A
  • Lean mice bacteria
  • White adipose tissue leptin
  • High levels of serotonin transporter
  • Ciliary neurotrophic factor (CNTF)
  • Low fat diet
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7
Q

Symptoms of cushing syndrome? (3)

A
  • Obesity
  • Glucose intolerance
  • Hypertension
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8
Q

Non shivering thermogenesis can be stimulated by?

Agonists/antagonist?

A
  • Adrenergic sympathetic neurons acting on β3 receptors on brown fat.
  • β3 agonists: CL316,243
  • Increased β1 adrenergic signalling can compensate
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9
Q

What are cholecystokinin-1 knockout rats? (3)

A

CCK KO mice = Otsuka–Long–Evans–Tokushima Fatty (OLETF) rats

  • They become obese and develop non-insulin dependent diabetes mellitus.
  • OLETF rats are hyperphagic with characteristic large increase in meal size with a decrease in meal frequency.
  • OLETF rats have elevated hypothalamic NPY mRNA expression, this can be prevented by increased physical activity.
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10
Q

Apart from CB1 and CB2 receptors, what other things are cellular targets of cannabinoids? (3)

A
  • Glycine receptor channels
  • The receptor encoded by GPR55 gene responds to endogenous cannabinoids
  • The presence of another putative cannabinoid receptor CB3 was suggested in hippocampus.
  • TRPV1 (capsaicin) channel (anandamide, endogenous cannabinoid, is agonist)
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11
Q

Describe mechanisms leading to methamphetamine toxicity (3)

A

Processes increasing highly neurotoxic cellular concentration of dopamine.

  • Downregulation of VMAT2
  • Upregulation of tyrosine hydroxylase
  • Inhibition of MAO

Sustained dopamine damages cellular proteins through interactions with cysteine

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12
Q

Describe opioid mediated negative feedback in mesolimbic pathway

A

κ receptors (dynorphin) mediate dysphoric activities of both k opioids and cannabinoids and oppose μ receptors in regulating the hedonic tone.

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13
Q

Why is development of a heroin vaccine so challenging? (2)

A
  • Produces number of active metabolites

- It stays in circulation for a pretty long time

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14
Q

Descirbe abnormalities from CB1 (3) and CB2 (2) KO in mice

A

CB1 KO

  • Reduced locomotor activity and hypoalgesia
  • Impairment of learning and memory and accelerated age-dependent loss of hippocampal neurons
  • No alcohol withdrawal symptoms

CB2 KO

  • Pain sensitivity
  • Bone loss
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15
Q

Describe the possible role of the insular cortex in the addiction to psychostimulants

A

Nicotine addiction is thought to be mediated in right anterior insular cortex

This part of cortex is stimualted by noxious stimuli

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16
Q

What can CB2 KO mice tell us about possible future therapies targeting these receptors?

A
  • KO produces mouse aversions in plus mazes, indicating that CB2 receptors in the
    brain can modify behavior
17
Q

What are the effects of alcohol dehydrogenase and aldehyde on alcohol consumption?

A

Aberrant aldehyde dehydrogenase and alcohol dehydrogenase (ALDH22 and ADH22 alleles) lead to the accumulation of alcohol’s metabolite, acetaldehyde, when a person drinks alcohol. This toxic compound produces nausea, flushing, dizziness, and other unpleasant effects, and slow alcohol metabolizers avoid excessive drinking.

Disulfiram (Calcium carbimide) blocks acetaldehyde metabolism – producing nausea, dizziness, and other unpleasant effects

18
Q

Explain the differential development of tolerance to opioids (eg. tolerance presents differently for different opioids)

A

Eg. Huge tolerance in opiate abusers, opiates for pain can be kept at same level for months.

  • Phosphorylation of protein kinase C can lead to G protein uncoupling. β-arrestins binding to phosphorylated receptors causes endocytosis of receptor.
  • Opioids differ in their ability to internalize opioid receptors (trafficking). Since internalization followed by recycling causes a re-sensitization of the receptors, opiates that don’t induce internalization show a lower development of tolerance.
  • Opioids with a lower intrinsic activity, such as morphine or the partial agonist buprenorphine have to occupy a larger fraction of opioid receptors to produce the same effect. These opioids show therefore a faster tolerance development than opioids with a higher number of spare receptors (spare receptor hypothesis)
19
Q

Heroin or opium and why. Dangerous

A

Heroin is made by morphine diacetylation.

  • It is more dangerous because it crosses the BBB quicker
  • It is metabolized into different parts, which can take a long time to clear from the system
  • It is more addictive (best answer)
20
Q

List 8 orexigenic (appetite stimulating) mediators

A
  • NPY
  • AgRP
  • MCH
  • Orexins (act via OX1)
  • Syndecans
  • Cannabinoids
  • Ghrelin
  • Gastric inhibitory peptide (GIP)
21
Q

List two biomarkers of alcohol abuse

A
  • Erythrocyte volume

- 5-HT metabolites in blood

22
Q

Effects of overexpression of CRF in mice?

A

Acts on receptors present in the anterior pituitary stimulates release of ACTH (HPA axis activation).

CRF over-expressing mice accumulate visceral fat and show Cushing’s-like symptoms, and also develop alopecia (patches of skin without hairs)

23
Q

What is common feature of NPY, PYY and pancreatic peptide?

A

Y1, Y2, Y4, Y5 and Y6 receptors mediate the actions of these peptides

NPY receptor subtypes Y1 and Y5 stimulate feeding while Y2 and Y4 inhibit appetite.

24
Q

Which drug of abuse is most neurotoxic?

A

???

25
Q

How are hallucinogens classifed

A

Hallucinogens that act via serotonergic receptors activation can be classified into two main categories: tryptamines (eg. psylocibin, LSD) and phenethylamines (eg. mescaline). All are agonists of the 5-HT2A receptors.

26
Q

List some actions of CB2 agonists

A
  • Dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion and cocaine-enhanced accumbens extracellular dopamine
  • Useful to prevent osteoporosis. Positive effects were observed in laboratory animals with ovariectomy-induced bone loss.
  • prevents the activation of microglia in rodent models of Alzheimer’s disease and reduces the volume of infarcts (necrosis) by 30% in a rodent occlusion model of stroke. They show also positive effect in treatment of allergy, inflammation and MS (autoimmune disorder that results in demyelination of neurons). CB2- selective agonists also suppresses hyperalgesia.
  • CB2 receptor agonist JWH015 significantly protects retinal pigment epithelial (RPE) cells which provide trophic support to photoreceptor cells in the eye. RPE cell death is observed in the age-related macular degeneration (AMD) and also in the retinitis-pigmentosa. Therefore, CB2-selective agonists also have potential therapeutic use in preventing the onset or progression of vision loss.
  • CB2-selective agonists stimulate progenitor cell proliferation in vivo, with this effect being more pronounced in older animals indicating that agonists of CB2 can be useful in regenerative medicine.
27
Q

Which drug of abuse is the highest cause of death?

A

Tobacco

28
Q

True or false? Mescaline is a tryptamine hallucinogen?

A

false

It is a phenethylamine

29
Q

List the tryptamine (3) and phenethylamines (3) hallucinogens

A

Tryptamine

  • Serotonin
  • DMT
  • Psilocybin/psilocin

Phenethylamines

  • MDMT
  • Mescaline
  • LSD
30
Q

Does peptide YY increase or decrease feeding?

A

It is secreted after ingesting food and inhibits further feeding.

31
Q

What are some similarities and differences between cocaine and methamphetamine?

A
  • MA creates stronger and longer lasting effects than cocaine
  • in part because cocaine is metabolized almost completely in the body whereas a large percentage of MA remains intact and active in the body longer
  • Due to chronic levels of MA staying in the body longer, adverse effects such as psychosis are more commonly induced by MA than cocaine
  • cocaine blocks dopamine re-uptake, prolonging dopamine activity in the brain, whereas MA not only blocks dopamine re-uptake, it also increases the release of dopamine.
  • Cocaine is from plant, meth is synthetic
32
Q

What is observed when lacking MC3Rs (melanocortin receptor 3)?

A

More adipose tissue, but otherwise normal bodyweight.

MC4R polymorphism leads to obesity.

33
Q

Leptin inhibits appetite by ___?

A
  • Stimulating POMC neurons
  • Inhibiting AgRP neurons
  • Inhibiting NPY neurons
  • Stimulating POMC neurons

Molecular Neuroscience III (8 decks)

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