Final Review Flashcards
The chances to develop drug addiction are highest for what drug that we studied?
Tobacco (highest)
Chronic opioid use facilitates the release of what neurotransmitter?
GABA
What is the strongest opioid?
Enkephalins? (met and leu?)
Which receptor agonist, dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion and cocaine-enhanced accumbens extracellular dopamine in wild-type
CB2 agonist
Which substances mediate sphingolipid metabolism? How?
Cannabinoids modulate sphingolipid metabolising pathways by:
- Inducing sphingomyelin (SM) breakdown
- Increasing the levels of the second messenger ceramide.
What prevents obesity in mice? (5)
- Lean mice bacteria
- White adipose tissue leptin
- High levels of serotonin transporter
- Ciliary neurotrophic factor (CNTF)
- Low fat diet
Symptoms of cushing syndrome? (3)
- Obesity
- Glucose intolerance
- Hypertension
Non shivering thermogenesis can be stimulated by?
Agonists/antagonist?
- Adrenergic sympathetic neurons acting on β3 receptors on brown fat.
- β3 agonists: CL316,243
- Increased β1 adrenergic signalling can compensate
What are cholecystokinin-1 knockout rats? (3)
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.
Apart from CB1 and CB2 receptors, what other things are cellular targets of cannabinoids? (3)
- 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)
Describe mechanisms leading to methamphetamine toxicity (3)
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
Describe opioid mediated negative feedback in mesolimbic pathway
κ receptors (dynorphin) mediate dysphoric activities of both k opioids and cannabinoids and oppose μ receptors in regulating the hedonic tone.
Why is development of a heroin vaccine so challenging? (2)
- Produces number of active metabolites
- It stays in circulation for a pretty long time
Descirbe abnormalities from CB1 (3) and CB2 (2) KO in mice
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
Describe the possible role of the insular cortex in the addiction to psychostimulants
Nicotine addiction is thought to be mediated in right anterior insular cortex
This part of cortex is stimualted by noxious stimuli
What can CB2 KO mice tell us about possible future therapies targeting these receptors?
- KO produces mouse aversions in plus mazes, indicating that CB2 receptors in the
brain can modify behavior
What are the effects of alcohol dehydrogenase and aldehyde on alcohol consumption?
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
Explain the differential development of tolerance to opioids (eg. tolerance presents differently for different opioids)
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)
Heroin or opium and why. Dangerous
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)
List 8 orexigenic (appetite stimulating) mediators
- NPY
- AgRP
- MCH
- Orexins (act via OX1)
- Syndecans
- Cannabinoids
- Ghrelin
- Gastric inhibitory peptide (GIP)
List two biomarkers of alcohol abuse
- Erythrocyte volume
- 5-HT metabolites in blood
Effects of overexpression of CRF in mice?
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)
What is common feature of NPY, PYY and pancreatic peptide?
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.
Which drug of abuse is most neurotoxic?
???
