EB - Psychoactive Drugs I

Question 1

What are the characteristics of Human imaging techniques? (5)

Answer 1

• Non-invasive
• Longitudinal
• No intervention studies – hard to get to mechanisms
• Can see effect of drugs
• Certain types of information only

Question 2

What is CT (2), MRI (3) and DTI (1)?

Answer 2

CT - Computed tomography

• Spatial resolution: several mm
• E.g. ventricular size

MRI and fMRI - Magnetic resonance imaging

• Resolution less than 1 mm
• Reveals patterns of activity in the intact brain

Activity utilises oxygen – microvasculature increases blood flow to active regions
oxyhb:deoxyhb ratio increased

DTI - Diffusion tensor imaging

• Mapping pathways and investigating aberrant connectivity

Question 3

What are PET and SPECT?

Answer 3

PET is positron emission tomography

SPECT is single-photon emission computed tomography (main advantage does not require on site cyclotron)

Question 4

How are unstable positron emission isotopes created for PET? (3)

Answer 4

• Created in a cyclotron (e.g., O15 with a half-life of 2 min)
• Isotopes are injected and distribute according to the relative activity of brain regions
• Can estimate receptor levels

Question 5

What are the non-invasive techniques for monitoring brain activity? (2)

Answer 5

EEG: Electroencephalography

MEG: Magnetoencephalography

Question 6

What are indirect markers for changes in neurotransmitter function?

Answer 6

Levels of neurotransmitters/metabolites in:

1) Cerebrospinal fluid (very invasive)
2) Plasma
3) Urine (e.g., decreased DA and metabolites like HVA in Parkinson’s disease)
4) Binding to platelets

Question 7

What is measured during postmortem brain analysis? (3)

Answer 7

Imaging and biochemistry

• Includes analysis of protein (e.g. receptor) levels
• RNA levels
• Localisation of proteins/RNA

Question 8

What are the limitations of postmortem brain analysis? (5)

Answer 8

• Endpoint analysis only
• Time post-death to freeze/fix/analyze
• Variability between samples
• Cause of death
• Possible medication effects

Question 9

What are the applications of human tissue culture and electrophysiological analysis?

Answer 9

1) Provides insights into cellular functions

• The potential of induced pluripotent stem cells

2) Can study genetic changes associated with disease development

Question 10

What are some animal model animal organisms? (5)

Answer 10

• Drosophila
• C.elegans
• Mice
• Rats
• Primates

Question 11

What are the advantages (3) and disadvantages (1) of using animal models in research?

Answer 11

Advantages

• Malleable
• Drug screening
• Can do studies with multiple time points, interventions

Disadvantages

• Mimic some but not all human

Question 12

What are psychotomimetic drugs?

Answer 12

Cause profound changes in perception, mood, and behavior

Question 13

What are 3 examples of hallucinogens?

Answer 13

• Ayahuasca (active ingredient: harmaline)
• Peyote (active ingredient: mescaline)
• Magic mushrooms (active ingredient: psilocybin)

Question 14

Compare the potency and effects of natural vs. synthetic hallucinogens

Answer 14

Natural:

• Psilocybin:
  Dose - 250 µg/kg,
  Duration - 3 hrs
• Mescaline:
  Dose - 15 mg/kg,
  Duration - 12 hrs

Synthetic:

• LSD:
  Dose - 3 µg/kg,
  Duration - 10 hrs (most potent)

Question 15

What was the original purpose of synthesizing LSD? (2)

Answer 15

• Derived from ergotism (gangrene, psychosis) caused by contaminated rye bread
• Aimed to treat hemorrhage using substances similar to ergot alkaloids

Question 16

What are the effects of LSD? (3)

Answer 16

• Somatic
• Perceptual
• Psychological

Question 17

How does LSD affect the brain? (3)

Answer 17

• Interacts with serotonin receptors
• Decreases firing rate of raphe neurons (5-HT1A receptor)
• Increases activity in locus coeruleus neurons and subsets of neurons in the cortex

Question 17

What is the significance of cross-tolerance between LSD and mescaline? (3)

Answer 17

• This suggests that both psychotomimetics act at the same class of receptor site
• The structures of LSD and mescaline are similar to 5-HT
• Early in vitro pharmacological studies showed that LSD interacts with 5-HT receptors in the peripheral vasculature: 5-HT2 receptor antagonist

Question 18

What is the role of 5-HT2A receptors in the brain? (2)

Answer 18

• Highly expressed on pyramidal neurons in the cortex
• LSD increases activity of layer V pyramidal neurons

Question 19

What is the impact of LSD on sensory perception? (2)

Answer 19

• Alters pathways that process sensory information
• Interest in noradrenergic (LC) input to thalamus and cortex

Question 20

LSD Effects in humans (4)

Answer 20

• increased visual cortex cerebral blood flow
• expanded primary visual cortex functional connectivity
• correlated strongly with ratings of visual hallucinations
• decreased connectivity between the para hippocampus and retrosplenial cortex