Flashcards in Psychopharmacology Deck (16)
routes of admin
Intravenous – into the blood – compound can go anywhere – issues with crossing blood-brain layer
Intraperitoneal – into space around organs but not into stomach
Subcutaneous – under skin
Sublingual administration – under tongue
Inhalation – onto lung
Topical administration – cream
Intracerebral administration – where neuroscience done – drill hole into skull – syringe into part of brain – corresponding changes in behaviour
1. Route of administration
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
blood brain barrier
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
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
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
margin of safety/therapeutic index
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.
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
Tolerance over time so have to increase the dose
Psychoactive drugs act on receptors on neurons, which open ion channels, which change the electrical potential of the membrane and so change psychological experience.
drug effects on receptors
Inverse agonist – bind to receptor but make ion channel work in opposite way
Precursor – nutritional – stuff gets broken down – turns into ntm
Blocks receptors – agonists
Major acetylcholine projections are from the pedunculopontine nucleus, and the nucleus Basalis of Maynert but there are other minor cholinergic systems.
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.
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
SN-Striatum – imp for motor control
VTA-NA – plays role in addiction – pleasure centre
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
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.
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
ratbots - Talwar et al. (2002)
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.
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
Norepinephrine cells bodies are located in the locus coeruleus and project broadly across the whole brain.
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.
Phasic LC activation = attention to goal-relevant stimuli.
Oddball stimuli produce spikes in LC activation, and the P300 cortical activation in humans.
Alert when something unexpected occurs
300ms after stim = activation – P300
P300 and local coeruleus activation at same time
5HT cell bodies originate in Raphe nuclei in the brain stem and project to the spine, cerebellum, sub-cortex and cortex.
5HT is commonly understood to play a role in depression and mood. Antidepressant medications increase on 5HT via different mechanisms
Glutamate is responsible for changing synaptic weight and thus learning
50% of the brain cells use it – v. imp
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
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
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