Test 2 Flashcards
What is an antipsychotic?
class of drugs used to treat psychosis - They are mostly dirty drugs, which means they bind to more than one type of receptor, but the one action they all have in common is they directly block the dopamine D2 receptor (direct dopamine receptor antagonsists)
What are atypical antopsychotics?
bind to a lot of receptors and changes the activity of receptors in different ways
- Didn’t completely cure psychosis; there were side effects
What is psychosis?
an abnormal condition of the mind that results in difficulties determining what is real and what isn’t
- Affects around 1% of the population
- Symptoms may include delusions, hallucinations, incoherent speech, and behaviour that is inappropriate for the situation
What are direct serotonin receptor agonists (receptor activators)?
- Used recreationally to cause hallucinations
- Activate serotonin 2A receptors, which are inhibitory metabotropic receptors expressed by neurons all over the brain
- But other direct serotonin 2A receptor agonists do not cause hallucinations at all
- For a long time, people did not understand why some 5HT-2A receptor agonists caused massive hallucinations while others did nothing of the sort
What is biased agonism?
• When a metabotropic receptor ligand causes the receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different g protein
- Different ligands binding to each receptor
What are direct agonists/antagonists?
drugs that affect postsynaptic receptor activity by directly binding to postsynaptic receptors
What are indirect agonists/antagonists?
drugs that affect postsynaptic activity in an indirect manner; the proteins they bind to are not postsynaptic receptors
What is a receptor agonist?
drug that directly or indirectly increases the activity of postsynaptic receptor proteins
What are drugs?
exogenous chemicals that at low doses significantly alter the function of certain cells
What is a competitive agonist?
acts similarly to the endogenous NT; it activates the receptor by binding where the neurotransmitter normally binds
What is a competitive antagonist?
attaches to the same binding where the neurotransmitter normally binds, but it doesn’t activate the receptor
- Competitive antagonists are full antagonists
What will the competition for a binding site between an endogenous NT and an exogenous drug will depend on?
their relative concentrations and their affinity for the binding site
What is non-competitive binding?
• When a drug binds to a receptor at a site that does not interfere with the binding site of the principal ligand
- It’s possible for a NT to bind on one site of a receptor while a drug binds on another
What is a non-competitive agonist?
it fully or partially activates the receptor
What is a non-competitive antagonist?
fully blocks receptor activation; it doesn’t compete for the NT binding site
- It “wins” without competing by binding to an alternative site
What are allosteric modulators?
non-competitive drugs that only influence receptor activity when the NT is also bound to the receptor
What are negative allosteric modulators?
reduce the effect of the primary ligand
What are positive allosteric modulators?
amplify the effect of the primary ligand
What is Parkinson’s disease?
a neurological disorder that is characterized by tremors, rigidity of limbs, poor balance, and difficulty initiating movements
- It’s caused by the degeneration (death) of dopamine neurons in the midbrain
How is dopamine made?
Made from tyrosine –> (enzyme) –> L-DOPA –> (enzyme) –> dopamine
How are conventional NTs made?
made in axon terminals and are made from precursor molecules (generally from amino acids)
- In some cases, precursor molecules can be administered as drugs since they can increase the amount of NT that is made and released precursors act as receptor agonists
What is the synthesis of NT form precursor molecules is controlled by ?
Enzymes
- Some antagonists work by blocking these enzymes, thus reducing production of the NT so there is less in each vesicle
What is the clearance of NTs from the synapse is controlled by?
reuptake transporter proteins and enzymatic deactivation
What is the therapeutic index?
the ratio between the dose that produces desired effect in 50% of animals and the dose that produces toxic effects in 50% of animals
What is tolerance?
when an effect of the drug diminishes because of repeated administration
- The body’s attempt to compensate for the effects of the drug
- Not all drugs show the same degree of tolerance
- Withdrawal symptoms: opposite effect of the drug
What is sensitization?
when a drug becomes more and more effective through repeated use
What is a dopamine D2 receptor?
an inhibitory metabotropic receptor expressed by neurons all over the brain
What is affinity?
the probability and tightness of ligand-receptor binding (in most cases it’s the NT)
What is a CT scan?
- A computer assisted x-ray procedure is used to take a photo of the brain
- The x-ray bean is delivered from all angles and a computer translates the information received from the x-ray detector into a series of pictures of the skull and brain (the densest tissues)
- Relatively cheap and fast, the resolution is not great for soft tissue like brain
What is an MRI?
- Uses strong magnetic fields instead of x-rays
- When molecules of the body are in a strong magnetic field, the hydrogen atoms spin with a particular orientation
- A radiofrequency wave is then passed through the body, which knocks the hydrogen atoms out of their orientation
- As they return to the orientation set up by the magnet, they emit their own radio waves that are detected by the scanner
- The scanner can estimate the density of hydrogen atoms in each area of the brain (they are most prevalent in fat and water) by calculating the amount of radio waves that come out of each region after each pulse of radio wave energy is delivered
- RESULT: high spatial resolution, 3-dimensional image of the brain
What is diffusion tensor imaging (DTI)?
- An MRI technique that measures the direction and speed of the diffusion of water molecules
- Used to identify axon tracts
- Colors indicate the direction of water molecule diffusion
What is an fMRI?
- We can see the flow of oxygenated blood by determining where the iron atom in hemoglobin is bound to oxygen and where it is not (correlates with neural activity)
- Technique is popular because it doesn’t use needles, surgery, or radioactivity
- It provides both structural and functional information with decent spatial resolution and temporal resolution
What is a PET scan?
- The person is injected with radioactive compound to detect changes in energy use over time
- The computer determines which regions of the brain have taken up the radioactive substance and produces a picture of the brain showing different activity levels
- early studies used 2-DG, but now we use L-DOPA or radioactive ligands
What is 2-DG?
Similar to glucose, since it is taken up by energy consuming cells in the body
- However, 2-DG is not broken down (metabolized) as easily as sugar is, so it stays around for hours
What is L-DOPA?
- L-Dopa is picked up by dopamine neurons, converted into dopamine, and released as normal
- With a PET machine it’s possible to see where the radioactive dopamine went
What are macroelectrodes?
- Used to record activity of a large number of neurons in a particular region of the brain
- Measure the effect of action potentials and post synaptic potentials (synaptic transmission) from millions of cells located around the electrode
- They are attached to an amplifier which records an electroencephalogram
What is an EEG?
Provides a measure of gross activity in the brain
- Provide a diagnostic tool which particular states of consciousness or types of cerebral atrophy are associated with specific patterns of EEG waveforms
What is an experimental ablation (lesion study)?
involves the removal or destruction of a portion of the brain, presumably the functions that can no longer be performed following the surgery are the ones the brain region normally controls
What are radiofrequency lesions?
Small lesions can be made by passing radiofrequency current through a metal wire that is insulated everywhere but the tip
- This electric current produce heat that burns cells around the tip of the wire
- The size and shape of the lesion is determined by the duration and intensity of the current
• Downside: axons just passing through will also be burned
What is a excitotoxic lesion?
Brian lesion produced by intracerebral injection of a glutamate receptor agonist
- cause so much excitation and calcium influx that the affected neurons often undergo apoptosis
- axons passing through are usually spared
What is a sham lesion?
Placebo procedure that duplicates all steps of producing brain lesion except it doesn’t cause extensive brain damage
What is a reversible lesion?
A temporary brain lesion that can be achieved by injecting drugs that block or reduce neural activity in a given region
To target cell bodies, what do drugs need to do?
the drugs need to target receptor proteins, not the proteins in action potential (ex: GABA receptor agonists)
What are microelectrodes?
Thin metal wires with a fine tip that can record the electrical activity of a single neuron (known as single-unit recording)
- Electrodes are implanted in the brains of animals using stereotaxic surgery
- The wires are connected to a socket and the animals can be ‘plugged in’ to a recording system
What is electrical stimulation?
Involves passing an electrical current through a wire inserted into the brain
- This will affect everything in the area (cell bodies and fibers of passage)
- Some electrical stimulation patterns (often very high frequencies) counterintuitively, tend to produce the same behavioural effect as lesioning the brain area
- Depolarizes everything
What is chemical stimulation?
Achieved with drugs
- In rodents, drugs are often administered through a guide cannula (hollow tube)
- Anesthetics can be injected to shut down all neural activity
- Alternatively, the drug may interact with receptor proteins, which will avoid the fibers of passage
What are optogenetics?
The use of light to control neurons which have been made sensitive to light through the introduction of foreign DNA
This foreign DNA encodes opsins
What are opsins?
Light-sensitive proteins
- The opsins we have in our eye are metabotropic receptors that operate with a 30-millisecond delay
- Often ion channels that open and close instantly in response to light
- The original ones were discovered in bacteria in different parts of the world
What is a virus?
Small infectious agent that replicates inside the cells of other organisms
- They cannot replicate without the help of others and they can’t read their own DNA; they inject it into a cell
- The DNA of a virus encodes instructions on how to make more virus
What is a replication deficient virus?
A virus that can’t do anything
- This happens when we remove the DNA from the virus
What is GCaMP?
Researchers modified GFP causing it to bind calcium and fluoresce much brighter when it does
- monitoring GCaMP fluorescence is a good way to measure neural activity (in cells made to express GCaMP protein)
