Psychopharmacology

Question 1

routes of admin

Answer 1

Intravenous – into the blood – compound can go anywhere – issues with crossing blood-brain layer

Intraperitoneal – into space around organs but not into stomach

Intramuscular

Subcutaneous – under skin

Oral administration

Sublingual administration – under tongue

Intrarectal administration

Inhalation – onto lung

Intranasal (insufflation)

Topical administration – cream

Intracerebral administration – where neuroscience done – drill hole into skull – syringe into part of brain – corresponding changes in behaviour

Intracerebroventricular

Question 2

bioavailability

Answer 2

determined by:

1. Route of administration
2. Dose
3. Rate – usually rate of injection
4. Absorption – sometimes cannot get past membranes
5. Elimination – enzymatic breakdown
6. Kinetics – change in bioavailability over time

Drug has to be available to substrate in order to work

see notes

Question 3

blood brain barrier

Answer 3

Blood brain barrier preserves the internal environment of the brain, and will screen out most foreign agents.

Specialised skin cells

Vary blood supply into the brain

Some hormones actively transported – cant get past barrier without further transporters

4 nanometre pores for water to diffuse passively – crucial to keep the brain hydrated

Some drugs only work if injected straight into brain, not body – cant get past barrier

Question 4

dose-response curve

Answer 4

Plots the dose of the drug against is measured effect.

Psychoactive effects tend to show S shaped curves due to upper limit of neural firing rates

see notes

ED50 – effective dose 50% - where drug produces 50% of max effect – need a reference point to compare different drugs

Limiting process of output of cell

Fire too much – cytotoxic death – why they have limiting step

Question 5

margin of safety/therapeutic index

Answer 5

Is the difference between the dose that produces the 50% maximum therapeutic effect, and the dose that produces the 50% adverse effect, expressed as a ratio.

see notes

Morphine used as painkiller

Produce max pain relief but minimum resp depression

e.g. 5mm/kg between ED50 for good result before hit ED50 for poor effect

see notes

Tolerance over time so have to increase the dose

Question 6

receptors

Answer 6

Psychoactive drugs act on receptors on neurons, which open ion channels, which change the electrical potential of the membrane and so change psychological experience.

see notes

Question 7

drug effects on receptors

Answer 7

see notes

Inverse agonist – bind to receptor but make ion channel work in opposite way

see notes

Precursor – nutritional – stuff gets broken down – turns into ntm

Blocks receptors – agonists

Question 8

acetylcholine

Answer 8

Major acetylcholine projections are from the pedunculopontine nucleus, and the nucleus Basalis of Maynert but there are other minor cholinergic systems.

see notes

Ntm systems have cell bodies which project to different areas

Thalamus = junction box – project into the 2 hemispheres

2 anatomically distinct systems

Acetylcholine increases the signal to noise ratio in the firing rate to the specific stimulus to which the neuron is tuned.

see notes

Project to visual cortex

Neurons always fire at basal rate

Tuning curve – only respond to specific stim

Tuning of cells responses

Deep brain stimulation of the pedunculopontine acetylcholine neuron is patients with Parkinson’s disease produced sudden onset sleep and dreaming

Stimulation – could produce immediate sleep or w=switch straight into REM sleep or narcolepsy (dream state) or produce waking

Question 9

dopamine

Answer 9

Nigrostriatal system
SN-Striatum – imp for motor control

Mesolimbic system
VTA-NA – plays role in addiction – pleasure centre

Mesocortical system
VTA-Frontal cortex – role in neg symptoms of Sz – disengage from everything - change long term mental representation of the world

NA – reward modifies voluntary behav

see notes

Question 10

electrical self-stim

Answer 10

Rats quickly learn to self-administer electrical stimulation of the medial forebrain bundle, the middle of the mesolimbic dopamine pathway from the VTA to nucleus accumbens.

see slides

Stick electrodes in rats brain

Stim when in diff part of box

Go back to place in box – associated with pleasure

Press lever to get stim

Medial forebrain – max area with most about self-stim – pleasure centre – acts as reinforcer

Question 11

ratbots - Talwar et al. (2002)

Answer 11

Rewarding rats with medial forebrain bundle stimulation for moving in a particular direction in response to virtual whisker stimulation, achieves an incredible level of control over the rats’ movement.

see slides

Whiskers highly sensitive

Stim feels like whisker touch – turn the same side as the touch

If does move – stim MFB = reward – quickly learns to do this

When moves forward = intermittent reward

Question 12

norepinephrine (noradrenaline)

Answer 12

Norepinephrine cells bodies are located in the locus coeruleus and project broadly across the whole brain.

see notes

Projects into cortex, sub-cortex, cerebellum and down the spine

Neuro-modulator – one cell group has broad effect on range of brain tissue

The locus coeruleus noradrenaline system is thought to play two roles in attention.
1. Baseline LC activation = alertness.

see notes

Phasic LC activation = attention to goal-relevant stimuli.

Oddball stimuli produce spikes in LC activation, and the P300 cortical activation in humans.

see slides

Alert when something unexpected occurs

300ms after stim = activation – P300

P300 and local coeruleus activation at same time

Question 13

serotonin (5HT)

Answer 13

5HT cell bodies originate in Raphe nuclei in the brain stem and project to the spine, cerebellum, sub-cortex and cortex.

see notes

5HT is commonly understood to play a role in depression and mood. Antidepressant medications increase on 5HT via different mechanisms

see notes

Question 14

glutamate

Answer 14

Glutamate is responsible for changing synaptic weight and thus learning

50% of the brain cells use it – v. imp

Input-output machine

On the glutamate synpase

• AMPA and Kainate = fast excitatory transmission – info transduction – amount info down depends on no. receptors
• NMDA = synaptic weight change by modifying the number of AMPA receptors

see notes

Question 15

GABA

Answer 15

GABA plays a major role in inhibition, capping the upper limit of cell firing rate through Renshaw cells

Which cell has most activation = inhibits other cell more – select down to strongest signal

see notes

Counterpoint to glutamate

More activated cell is = more inhibits self – may set the cap of activation

Epilepsy is a failure of GABA inhibition to constrain excitatory loops in the brain. Most medications for epilepsy act to increase GABA inhibition, or decrease glutamate excitation

Question 16

endorphins (opiates)

Answer 16

Endorphins inhibit transmission of pain signals in peripheral nervous system, and the central nervous system

see notes

Endorphins released by the pituitary form part of the fight or flight stress response, and act on presynaptic opioid autoreceptors on pain signalling neurons.

see slides

Endorphins microinjected into the nucleus accumbens (terminal of the mesolimbic dopamine pathway) increase hedonic facial reactions to sweet flavour, and decrease aversive reactions to bitter flavour (in rats) suggesting a role in subjective euphoria.