Brain and Behaviour Lecture 4
Terms in this set (55)
The study of the effect of drugs on the nervous system and behaviour.
The changes a drug produces in an animal's physiological processes and behaviour. In the nervous system, most drugs affect synaptic transmission.
A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell.
A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell.
Sites of action
The locations at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells.
Main sites of action
1. production of neurotransmitters
2. storage and release of neurotransmitters
3. effects on receptors
4. effects on reuptake
Production of neurotransmitters (agonist)
The rate of synthesis and release of a neurotransmitter is increased when a precursor (drug e.g. L-dopa) is administered, in these cases the precursor serves as an agonist (more material to produce neurotransmitters).
Production of neurotransmitters (antagonist)
The steps in synthesis of neurotransmitters are controlled by enzymes. Therefore, if a drug inactivates one of these enzymes, it will prevent the neurotransmitter from being produced. Such a drug serves as an antagonist.
Storage and release of neurotransmitters
Neurotransmitters are stored in synaptic vesicles, which are transported to the presynaptic membrane, where the chemicals are released.
The storage of neurotransmitters in vesicles is accomplished by the same kind of transporter molecules that are responsible for reuptake of a neurotransmitter into a terminal button.
Drug effects on storage and release of NT
Some of the transporter molecules that fill synaptic vesicles can be blocked by a drug. Molecules of the drug bind with a particular site on the transporter and inactive it. Because the synaptic vesicles remain empty, nothing is released when the vesicles fuse with the presynaptic membrane. This drug serves as an antagonist.
Drug effects on receptors
Once a neurotransmitter has been released, it must stimulate the postsynaptic receptors. Some drugs bind with these receptors, just as the neurotransmitter does. Once a drug has bound with the receptor, it can serve as either an agonist or an antagonist.
A drug that binds with and activates a receptor. The drug mimics the effect of a neurotransmitter. An agonist will keep the ion channel open all the time. An antagonist will keep the ion channel closed.
A drug that attaches to a binding site on a receptor and facilitates the action of the receptor; does not interfere with the binding sites of the principal neurotransmitter. This is also known as non-competitive binding as they bind to the same channel as the neurotransmitter.
The process of termination of the postsynaptic potential. Two processes accomplish this task. The neurotransmitter can be taken back into the terminal buttons (reuptake) or they are destroyed by an enzyme.
Drug effect on reuptake
Molecules of the drug attach to the transporter molecules that are responsible for reuptake and inactivate them, thus blocking reuptake. This prolongs the presence of the neurotransmitter in the synaptic cleft (agonist).
Drug effect on destruction
Molecules of the drug bind with the enzyme that normally destroys the neurotransmitter and prevents the enzymes from working (agonist).
When experimenters want to investigate the behavioural effects of drugs in humans, they must use control groups whose members receive placebos, or they cannot be sure that the behavioural effects they observe were caused by specific effects of the drug (usually double blind trials).
The nocebo response, where people can feel worse after an intervention that should have no ill effect.
Other neurotransmitters, other than glutamate and GABA have modulating effects rather than information-transmitting effects. This means they tend to activate or inhibit entire circuits of neurons that are involved in particular brain functions (e.g. acetylcholine).
The primary neurotransmitter secreted by the efferent axons on the CNS. It is responsible for all muscular movement as well as regulating REM sleep and memory.
An ionotropic acetylcholine receptor stimulated by nicotine which causes depolarization. It can be blocked by curare (used in animals during surgery to cause paralysis).
A metobotropic acetylcholine receptor which produces parasympathetic nerve effects in the heart, smooth muscles and glands. It is blocked by atropine (creates a more frequent heartbeat).
An acetylcholine antagonist, prevents release by terminal buttons. It is used for paralysis of muscles (botox).
Black widow spider venom
a poison produced by the black widow spider that triggers the release of acetylcholine causing convulsions (muscle contractions).
Synapses that have acetylcholine transmitter.
Cholinergic synapse stages
1. An action potential arrives at the presynaptic membrane. Voltage gated calcium channels in the presynaptic membrane open, calcium ions enter the presynaptic neuron.
2. Calcium ions cause synaptic vesicles to fuse with the presynaptic membrane releasing acetylcholine into the synapatic cleft.
3. Acetylcholine diffuses across the synaptic cleft and binds to specific neuroreceptor sites in the post synaptic membrane.
4. Sodium channels open. Sodium ions diffuse into the postsynaptic membrane causing depolarization which may initiate an action potential.
5. Acetylcholinesterase (enzyme) breaks down acetylcholine. The product diffuses back into the presynaptic neuron where acetylcholine is resynthesised using ATP from the mitochondria.
Same stages as cholinergic synapses but in this case the postsynaptic membrane is the muscle fibre membrane (sarcolemma). Depolarization of the sarcolemma leads to contraction of the muscle fibre.
Dopamine, norepinephrine, epinephrine and serotonin are four neurotransmitters which belong to a family of compounds called monoamines. This is because the molecular structures of these substances are similar, some drugs affect the activity of all of them to some degree.
A neurotransmitters associated with reward that alters the decision-making area of the brain. It is also linked to regulating movement and controlling attention.
Pathway within the limbic system, within the ventral area of the midbrain, that is associated with feelings of reward in day-to-day life and the feelings of pleasure that lead to craving and addition. Activation of this pathway by addictive drugs leads to increase levels of dopamine.
A state in which an organism engages in compulsive behaviour, behaviour is reinforcing and linked to a loss of control for limiting intake.
A state in which organisms no longer respond to a drug. A higher dose is required to achieve the same effect.
A state in which organisms function normally only in the presence of a drug. It is manifested as a physical disturbance when the drug is withdrawn.
Tolerance and dependence are related to different circuits in the brain. So, it is possible to be dependent without being addicted e.g. morphine used by cancer patients.
a system of neurons originating in the substantia nigra and terminating in the basil ganglia. It plays a role in the control of movement.
Degeneration of this system is linked to diseases such as parkinson's disease treated by L-DOPA.
Starts in the ventral tegmental area and terminates in the nucleus accumbens, amygdala and hippocampus. It plays a role in the reinforcing effects of drugs that are commonly abused.
1. Dopamine (neurotransmitter) is released into the synaptic cleft from vesicles in the presynaptic neuron.
2. The dopamine binds to the dopamine receptors on the postsynaptic membrane.
3. The dopamine binds to the postsynaptic cell causing the release of more dopamine. Which triggers the release of endorphins.
Cocaine inhibits the reuptake of dopamine. This leads to increased activation of the reward system.
Metabolic activity (cocaine)
In PET scans a brain is shown to be less active on cocaine. This means there is less energy/glucose consumption.
Plays a role in regulation of mood, pain and the control of eating, sleep, dreaming and arousal.
Stimulates centers of the sympathetic nervous system in the midbrain which leads to pupillary dilation, increase in body temperature, and rise in blood-sugar level. It also has a serotonin blocking effect. It also has psychedelic effects.
a drug that serves as a noradrenergic and serotonergic agonist, also known as "ecstasy"; has excitatory and hallucinogenic effects.
Ecstasy effects on serotonin transporters
1. prevents reuptake
2. Works in reverse - brings more 5-HT (serotonin) to the synapse as it signals for more.
Short-term effects of ecstasy
During ecstasy there is a feeling of elevated mood, whilst after ecstasy there is feelings of depression, irritability and often disturbed behaviour.
Long-term effects of ecstasy
Serotonin present in cerebral cortex neurons is decreased 2 weeks after ecstasy after 7 years of use serotonin synapses can recover but not fully. This can present issues with verbal and visual memory. This is because ecstasy causes degeneration of serotonin nerve terminals.
Low serotonin levels are believed to be the cause of many cases of mild to severe depression which can lead to symptoms such as anxiety, apathy, fear, feelings of worthlessness, insomnia and fatigue.
If depression arises from this, then pharmaceutical agents that increase the amount of serotonin in the brain should be helpful. Anti-depressant medication increase serotonin levels at the synapse by blocking the reuptake of serotonin in the presynaptic cell.
Both a hormone and a neurotransmitter. As a hormone, secreted by the adrenal gland. It works alongside epinephrine / adrenaline to give the body sudden energy in times of stress (fight or flight response).
Medications that inhibit the reuptake of NE can treat depression.
These are the most common neurotransmitters in the CNS: glutamate, gamma-aminobutyric acid (GABA), and glycine.
An amino acid, the most important excitatory neurotransmitter in the brain. The NMDA receptor is a specialized ionotropic glutamate receptor.
GABA (gamma-aminobutyric acid)
An amino acid. GABA is the most important inhibitory neurotransmitter in the brain and glycine in the spinal cord. It is involved in many different functions. An imbalance in GABA is relevant to bipolar disorder, schizophrenia and anxiety disorder.
GABA brake system
GABA provides the necessary inhibitory effect that we need in order to block out excessive brain activity that in depression may lead to excessive negative thinking.
For example, benzodiazepine is a category of anxiolytic drugs: an indirect agonist for the GABA receptor. These drugs are used for their tranquilizing effects.
Cocaine blocks the reuptake of dopamine through the uptake pump, increasing the levels of the neurotransmitters in the synaptic cleft.
Dopamine binds to the receptors on the postsynaptic neuron causing an action potential. This produces the feeling of anticipation for reward.
Endorphin (opiate) bind to the opiate receptors on the postsynaptic neuron, producing positive feelings.