NEUROTRANSMITTERS AND SYNAPSESOption E.4

Assessment Statements E.4.1 State that some presynaptic neurons excite

postsynaptic transmission and others inhibit postsynaptic transmission.

E.4.2 Explain how decision-making in the CNS can result from the interaction between the activities of excitatory and inhibitory presynaptic neurons at synapses.

E.4.3 Explain how psychoactive drugs affect the brain and personality by either increasing or decreasing postsynaptic transmission.

E.4.4 List three examples of excitatory and three examples of inhibitory psychoactive drugs.

E.4.5 Explain the effects of THC and cocaine in terms of their action at synapses in the brain.

E.4.6 Discuss the causes of addiction, including genetic predisposition, social factors and dopamine secretion.

Synaptic transmissionNeurons communicate with each other chemically across a space called a synapseOne side of the synapse is the presynaptic membrane of the sending neuron and on the other side of the synapse is the postsynaptic membrane of the receiving neuronMolecule which moves across the space (synaptic cleft) between the two membranes is called a neurotransmitterSpecific neurotransmitter is received by a specific receptor

Excitation and Inhibition Some neurotransmitters are excitatory and

stimulate the next neuron to forward the message

Do this by increasing the permeability of the postsynaptic membrane to positive ions, making it easier for positive ions to move in

Some neurotransmitters are inhibitory and cause the positive ions to move out of the postsynaptic cell

Positive ions move back in to the synaptic cleft chemically depressing the postsynaptic cell and makes it much harder to excite

Decision making in the CNS Impulse which moves down

the presynaptic neuron is called the action potential

As action potential reaches axon bulb, calcium ions rush into the end of the neuron

Vesicles containing neurotransmitters fuse with the presynaptic membrane

Neurotransmitter released into the synaptic cleft

Neurotransmitter binds to specific receptors on the postsynaptic membrane

Receptors let ions enter or leave when the neurotransmitter binds to them

Excitatory neurotransmitters One example: acetylcholine Generates action potential Increases permeability of the postsynaptic membrane to

positive ions Causes positive sodium ions to diffuse into the postsynaptic

neuron Localized depolarization occurs Inside of neuron develops a net positive charge compared

to the outside Depolarization continues as sodium ions diffuse to the next

area of the neuron Impulse is carried along the nerve If threshold is not met, the neuron does not carry the

impulse to the next neuron

Inhibitory neurotransmitters Example: GABA Inhibit action potentials Causes hyperpolarization of the neuron Inside of the neuron becomes more negative

making it difficult for an action potential to be generated

GABA binds to specific receptor Causes negatively charged chloride ions to move

across the postsynaptic membrane into the postsynaptic cell OR it can cause positively charged K+ ions to move out of the postsynaptic neuron

Movement of Cl- into the neuron or K+ out causes hyperpolarization

Putting it together

A neuron is always on the receiving end of many excitatory and inhibitory stimuli

Neuron sums up the signals If the sum of the signals is inhibitory

then the axon does not fire If the sum of the signals is excitatory,

the axon fires Summation of the messages is the

way that decisions are made by the CNS

Cholinergic synapses

Acetylcholine is released by all motor neurons and activates skeletal muscle

If it remained in the synapse, the postsynaptic membrane would go on firing indefinitely

Acetylcholinesterase breaks it down Acetylcholine is involved in the

parasympathetic nervous system Causes relaxation rather than flight

Nicotine stimulates transmission in cholinergic synapses which is why it has a calming effect on the body and personality

People addicted to nicotine become very agitated if they cannot have a cigarette

Adrenergic synapses

Noradrenaline depolarizes the postsynaptic neuron

Noradrenaline is involved in the sympathetic sysem

It causes a “fight or flight” reaction Cocaine and amphetamines both

cause increased alertness, energy and euphoria

Cholinergic Adrenergic

Neurotransmitter Acetylcholine (Ach) Noradrenaline

System Parasympathetic Sympathetic

Effect on mood Calming Increased energy, alertness, and euphoria

Drugs increasing transmission at synapse

Nicotine Cocaine and amphetamines

Effect of drugs on the brainCan alter your mood or your emotional stateExcitatory drugs (nicotine, coaaine, amphetamine) increase nerve transmissionInhibitory drugs (benzodiazepines, alcohol, and THC) decrease the likelihood of nerve transmissionDrugs can change synaptic transmission in the following ways:

Block a receptor for a neurotransmitter (structure similar to the transmitter)

Block release of neurotransmitter from the presynaptic membrane

Enhance neurotransmission by mimicking a neurotransmitter

Block removal of neurotransmitter from the synapse and prolong the effect of the neurotransmitter

Excitatory drugs and how they actNicotine mimics acetylcholine (Ach)Acts on the cholinergic synapses of the body and the brain to cause a calming effectAfter Ach is received by the receptors, it is broken down by acetylcholinesterase but it cannot break down nicotineThis excites the postsynaptic neuron and it begins to fire, releasing a molecule called dopamineDopamine gives you a feeling of pleasure

Cocaine stimulates transmission at adrenergic synapses and causes alertness and euphoria

Causes dopamine releaseCocaine blocks removal of

dopamine from the synapse so that it builds up

Leads to overstimulation of the postsynaptic neuron

Leads to euphoria

Both of these drugs causes addiction

Amphetamine stimulates transmission at adrenergic synapses and gives increased energy and alertnessAmphetamine acts by passing directly into the nerve cells which carry dopamine and noradrenalineIt moves directly into the vesicles of the presynaptic neuron and causes their release into the synaptic cleftNormally these would be broken down, but amphetamines interfere with breakdown

High concentrations of dopamine cause euphoria and high concentrations of noradrenaline may be responsible for the alertness and high energy effect

Inhibitory drugs and how they act Benzodiaizepine reduces anxiety Can be used against epileptic

seizures Modulates the activity of GABA which

is the main inhibitory neurotransmitter

When GABA binds to the postsynaptic membrane, it causes Cl-to enter the neuron

Causes hyperpolarization and resists firing

B increases the binding of GABA to the receptor and therefore greater hyperpolarization

Alcohol acts similarly to B in that it increases the binding of GABA to the postsynaptic membrane

Decreases activity of glutamate, an excitatory neurotransmitter

Alcohol helps to increase the release of dopamine by a process which is not well understood

Appears to stop the activity of the enzyme which breaks down dopamine in the synaptic cleft

Tetrahydrocannabinol (THC) is the main pschoactive chemical in marijuana

THC mimics the neurotransmitter, anandamide

THC binds to the same receptor and cause the postsynaptic neuron to be hyperpolarized

Anandamide may play a role in memory functions, such as eliminating information from our memory that is not needed

Marijuana disrupts short-term memory in humans

THC effects

Feelings of relaxation, lightheadedness, haziness

Decrease in learning, coordination, problem-solving, and short-term memory

Stays in synapse longer than anandamide

High concentrations of receptors found in hippocampus (short-term memory); cerebellum (coordination)

Cocaine effects

Euphoria, talkativeness, increase in mental alertness

Temporary decrease in the need for food and sleep

Large amts. Cause erratic and violent behavior

Sustains level of dopamine in the synapse

Causes of addiction

Body develops a tolerance and needs more of the drug to produce the same result

Chemical dependency is caused by drug “rewiring the brain” and becoming an essential biochemical in the body

Role of abused drugs is to stimulate the reward pathway located in the brain

Withdrawal symptoms Anxiety, depression,

craving Seizures, severe

shaking

Continued addiction Lung damage Risk of contracting

HIV, hepatitis B and C

Kidney disease

Genetic predisposition Studies in male twins find that when

one twin suffers an addiction to alcohol or drugs, the rate of addiction in the second twin is 50% greater among identical twins than among fraternal twins

Other experiments indicate that a genetically determined deficiency of dopamine receptors predisposes certain people to addiction

Persons who become addicted to drugs that increase dopamine levels do so to compensate for that deficiency

Social factors of addiction

Family addiction, family parenting skills, mental health problems of family or child

Often related to peer group; users teach new users what effects to expect and what altered state is desirable

Alcohol at social gatherings fosters the paradigm that it must be available to have a party

Alcohol very rare in Saudi Arabia since it is prohibited

Dopamine secretion

Neurotransmitter which activates the reward pathway and gives us a sense of pleasure or satisfaction

During cocaine use, dopamine builds up in the synapse

Over-stimulation decreases the number of receptors and the remaining receptors become less sensitive to dopamine (desensitization or tolerance)

With tolerance, exposure to the drug causes less response that it previously caused

More and more of the drug is needed to have even the normal sense of well-being

Type of neuroadaptive change

Knockout mice

Genetically manipulated mice addicted to cocaine

Studies show that glutamate may oversee the learning and memories which lead to cocaine-seeking

Mouse party