Drugs Of Abuse And Cognitive Decline

Question 1

What drugs affect the brain? (5)

Answer 1

Anabolic androgenic steroids (AAS)

Opioids

Central stim.

GHB

THC

Question 2

AAS may affect cognitive function - water rat maze (2009) (2)

Answer 2

reports indicating that steroids induce impairments in cognitive function in AAS abusers

Experimental animal studies using water maze (MWM) demonstrated that AAS may produce negative effects on cognition - Male rats exhibited impaired
Performance in the Morris water maze (MWM) following exposure to the AAS nandrolone decanoate.

Question 3

AAS’ effects on hippocampus

Answer 3

AAS causes reduction in the number of neurons in hippocampus, parietal cortex and prefrontal cortex regions and increases oxidative damage

Question 4

Long-term use of AAS may give rise to cognitive impairments - 2013 study (3)

Answer 4

A study with 31 male AAS users and 13 non-AAS-using weightlifters age 29-55.

Five cognitive tests from the computerized CANTAB battery (Pattern Recognition Memory, Verbal Recognition Memory, Paired Associates Learning, Choice Reaction Time, and Rapid Visual Information Processing).

The AAS users showed substantial and sig. deficits in the two visuospatial tests compared to the controls

Question 5

AAS - Amygdala enlargement study (3)

Answer 5

A multimodal MRI study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure.

Result indicated that long-term AAS use is associated with right amygdala enlargement and reduced right amygdala resting-state coupling with a number of brain regions.

Further support that AAS use impairs visuospatial memory.

Question 6

So what is the AAS trend after 10/20yrs?

Answer 6

cognitive decline of memory following the use of steroids in 60yrs or so

Question 7

Opiates and cognition? (3)

Answer 7

• get nerve cells from rats (hippo = memory) + treat w/ opioids

1) morphine = cell death w/ increasing conc.

2) methadone (heroin sub. therapy) = overtime -ve effect on nerve cells: increasing conc = get worse

Long-term use of opiates may lead to negative effects on learning and memory

Question 8

GH in learning and memory function (3)

Answer 8

1. GH replacement therapy produces improved short term+ long term memory
2. GH affects cognitive functions in rats
3. GH improves cognitive capabilities in hypophysis-ectomized rats - NMDA subunits are up-regulated

Question 9

Proposed pathway of how GH interacts w/ excitatory circuits in the brain (7)

Answer 9

1) goes through IGF1 or 2
2) IGF type 1 receptor
3) GluN1 etc. (PSD-95)
4) cAMP
5) PKA
6) CREB
7) new proteins + form. of new synapses = inc. LTP + improved memory

Question 10

Growth hormone (GH) may reverse brain damages - 3 studies (3)

Answer 10

rat: w/ both Opiates and AAS:
1mM of morphine treated w/ GF = cells completely restored

human: 1 patient methadone for 6yrs = cog. decline - gave him GF = improved cognition = life standards

water maze: AAS - given GF fter and improved their ‘target zone crossing’

Question 11

Angiotensins recap (4)

Answer 11

1 + 2 = major BP peptides

inc. in angio 2 = bind to AT1 receptors = increase BP

hypertension treatment = AT1 antagonist

Ang II - 2 A.A’s = Ang 4 (no relation/effect on bp) but actually memory promoting effect

Question 12

Hippo nerve cells growth (3)

Answer 12

1) remove hippo nerve cells from rats + grown

2) staining/colouring synapse to help follow if more nerve cells connections are created

3) These increased synaptic contacts allow for greater communication
b/w neurons = this in turn facilitates learning and memory

The density of dendritic spines correlates extremely well with both the capacity to learn as well as a marker for acquired knowledge

Question 13

Ang 4 + nerve cells drug dev. (4)

Answer 13

peptide isn’t optimal to make drug - immediately degraded (orally) , injected - in but half-life =2/3mins = not pass BBB = X cog effect

= drug dev.
1) look at peptide - see studies that certain components needed for effect (e.g. tyrosine)

2) looked at substrates it binds to = oxytocin (longer half life - ring structure)

3)conserve these parts + cut off others + added ring structure

Question 14

Ang 4 + nerve cells drug dev. test - dendritic spines (3)

Answer 14

1) tested 1nM
= dendritic spines inc.

2) tested 10nM
= more dendritic spines inc.

3) tested 100nM
= even more dendritic spines inc.

Question 15

ang 4 analogues in animal studies (2)

Answer 15

rats y maze: (run + explore)
= compound has no effect on total motion
= but effect on attention score inc. = memory

Question 16

Do all steroid users become drug addicts that display aggressive behaviour? (3)

Answer 16

3 factors like w/ all drugs:

Increased risk of drug addiction/abuse if…
- Long-term use of AAS?
- Environmental factors?
- Vulnerability (genetics)?

probabilities and not everyone get addicted or anygry but dependent on these factors ^^^^