Een zeer interessant deel van het vak is topic 4 van Algemene Farmacologie over Psychoactive Drugs. Samen met topic 3 weet je nu precies hoe medicijnen het zenuwstelsel beïnvloeden en tot welke ziektebeelden dit kan leiden. Ook medicatie en schizofrenie wordt uitgebreid behandeld Een volledig over...
Alle afbeeldingen en figuren zijn afkomstig van colleges van het UMC Utrecht (BRON)
Topic 4 Psychoactive drugs
- Gain knowledge about the effects and mechanisms of action of different
psychoactive drugs (brain activity and changes)
- Study the process of screening new therapeutic drugs for treatment of brain
disorders, with emphasis on preclinical drug evaluation with animal models
Lecture 1: Introduction
What are psychoactive drugs?
Chemical substances that have an effect on the brain by changing neural transmission and
thereby changing brain function, which changes behaviour.
Psychoactive drugs affect brain function and therefore have a behavioural effect.
These drugs have to pass the blood-brain barrier which is composed of multiple cell layers.
The BBB protects the brain against chemical toxic substances. The BBB has a certain lipofility
and also there are transport proteins to transport brain drugs.
Psychoactive drugs are used for the following reasons:
1. Recreational use
a. This means that psychoactive drugs are taken by healthy people, the drugs
have a positive effect on how you feel. For example XTC: very lipofilic, will
immediate be taken up and the effect is immediate.
2. Therapeutic use
a. Pills of the doctor by prescription for a patient that suffers brain disorders and
shows symptoms of brain disfunction. Psychoactive drugs can restore brain
function to let the symptoms disappear.
There are several types of psychoactive drugs, they can be categorized by their effect:
Stimulants, depressants, hallucinogens.
Stimulants stimulate or increase brain activity by targeting the brain. You have
strong and weak stimulants. Examples: amphetamines, ritalin, cocaine, caffeine.
The complete opposite of stimulants are depressants, that depress or inhibit brain
activity. Make people calm or fall asleep or repress pain. Examples: diazepam (sleeping
pills), codeine, morphine.
Hallucinogens neither inhibit nor stimulate brain activity but they distort sensory
perceptions. Depending on dose or the situation, it can either stimulate or depress brain
function and have a hallucinogenic effect. Examples: marihuana, MDMA, LSD, ketamine.
How do psychoactive drugs influence brain activity?
They influence brain activity by altering synaptic neurotransmission. See link on blackboard
for basiscs of neurotransmission.
There is communication in the brain by neurons that secrete neurotranmitters which are
chemical substances. There are pre- and post-synaptic neurons that are chemically
stimulated by an action potential. Activation of the post-synaptic neuron leads to release of
neurotransmitters in the synaptic cleft by diffusion, binding of neurotransmitter to the post-
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, synaptic neuron (receptors on cell body or dendrites) leads to stimulation and also another
action potential, by adding up all EPSPs. This is how the signal is transported by chemical or
electric signals. This is the basis of brain function.
There are many different neurotransmitters in the brain:
- Fast neurotransmitters, 80%. These are called the amino acid neurotransmitters.
o Glutamate (50%) activates/initiates neuronal activity: excitatory.
o GABA (30%) is the main inhibitory neurotransmitter, it inhibits neuronal
activity.
o The balance between glutamate and GABA is important for whether there is
brain stimulation or inhibition.
- Slower neurotransmitters are present in the rest of the brain, which are
monoamines/neuromodulators. They can modulate the activity of GABA and
glutamate: increasing the effect of monoamines effect glutamates. The
monoamine systems are usually the target of psychoactive drugs.
o Catecholamines: dopamine, noradrenaline
o Serotonin
o Histamine
- Acetylcholine: this is either a fast neurotransmitters either a slow neurotransmitters,
depending on which receptor it targets.
- Other chemical messengers are neuropeptides, they are in low presence in the brain
and are often combined with monoamines or amino acids. They are the ultimate
modulators and they can change the activity of monoamines or of amino acids.
A neurotransmitter affects the next neuron because it changes the electricity signal.
There are two types of receptors in the CNS: metabotropic and ionotropic. Ionotropic causes
fast actions, metabotropic causes slower actions.
For example, amino acids glutamate and GABA both can bind to ionotropic and
metabotropic receptors. The monoamines predominantly bind to the metabotropic
receptors, only serotonin can also bind ionotropically. For acetylcholine it also depends
whether it binds ionotropic or metabotropic. There are many subtypes of receptors which
have different effects.
Brain function and neurotransmitters
Our higher functions, motor and cognitive behaviour and emotional processes, are
regulated by different regions in the brain. There are signaling circuits between the striatum,
thalamus and cortex – coloured in blue.
Every behavioural process involves a different circuit: CSTC-loops – cortex-striatum-
thalamus-cortex (so always back to the cortex). The neurotransmitters that are involved are
always the fast neurotransmitters glutamate or GABA. => This is the simple loop for complex
behaviour.
Monoamines are involved in signaling from the brainstem to the cortex and to the striatum
with their long projecting neurons: this is the red loop. They can affect the activity of the
loop, by changing glutamate or GABA signaling. By this, monoamines also have a great role
in higher functions of the brain: motor/cognitive/emotional behaviour.
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