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What are neurons?
Nerve cells that transmit information. All the neurons in our body form the nervous system.
How many neurons are there in the brain?
On average, 86 billion neurons are in the human brain.
If you stretched out all your neurons from end to end, how long would it measure?
160,000 km long (4 x around the planet)
What part of the neuron is the location where information from other neurons are received?
Dendrites - spiny tree-like bits
What are the dendrites attached to?
The soma or cell body - cell body protects the nucleus and cell contents
How does the soma / cell body carry out its function?
It protects the nucleus and cell contents by the phospholipid bilayer - maintains the negative charge within the cell (outside the cell it is positively charged)
What is the "engine room" of the neuron called?
The nucleus contains the genetic material which tells the cell what to do, what neurotransmitters to produce and what proteins to make
What is the gatekeeper of transmission in the neuron?
The axon hillock decides whether information received by the cell will be passed onto another cell depending on how much information it gets from other sources
How does the axon hillock decide whether information received will be passed on to another cell?
By graded potentials (sum all electrical energy received) which determines whether an action potential will be fired.
What part of the neuron conducts electrical signals from the cell body?
The axon is a long nerve fiber (can be over a metre long) does so.
What protects the axon?
The myelin sheath is a coating that insulates and protects the axon - it also allows the signal to travel faster
What produces the myelin sheath?
Schwann cells which are a type of microglea cell.
What helps the electrical signal in the neuron jump or continue down the axon?
The nodes of Ranvier which are bare bits of axon help the electrical signal jump or continue down the axon. Without the nodes, the signal would just dissipate.
What's at the very end of the neuron where the chemical signals are released?
Axon terminals or terminal buttons released the chemical messages. These chemical signals are called neurotransmitters and are sent to the next neuron.
What is the gap between neurons called where neurotransmitters pass through?
What is the clinical relevance of the myelin sheath?
Myelin sheath is produced by Schwann cells. The failure of Schwann cells causes axons to lose their myelination. Overtime, the myelin sheath disappears and the transmission speed of the signals reduce, preventing signals from coming through.
What are the 3 types of neurons by structure?
- Multipolar neuron (lots of dendrites) - same physiology as other neurons
- Bipolar neuron (two branches, one branch is the dendrite and the other is the axon)
- Unipolar neuron (still have dendrites but instead of axon hillock you have a trigger zone where it will be decided if an action potential is fired)
What are the 3 types of neurons by function?
- Sensory neurons - activated by sensory input e.g. being pinched
- Motor neurons - activated when you pull your hand away because the pinch was too strong
- Interneurons - connective neurons because they connect to other neurons - they don't connect to sensory environment (muscles) but just signal between neurons
What are the differences in signals produced by sensory and motor neurons?
- Sensory neurons - send info from periphery to CNS (brain) so produce afferent signals
- Motor neurons - send info from CNS (brain) to periphery so produce efferent signals
Where are sensory, motor and interneurons generally located in?
- Sensory - many different kinds of sensory neurons but you have vision (photoreceptors responding to light), somatic (mechanoreceptors responding to touch/pressure/temperature), auditory (stereocilia from hair cells responding to vibration)
- Motor - spinal chord - axon projects to the periphery to control muscles
- Interneurons - pretty much located everywhere but all neurons within the brain are interneurons - involved in higher order processing (memory & cognition)
What structure do sensory, motor and interneurons generally have?
- Sensory - unipolar or bipolarMotor - multipolarInterneuron - multipolar
What is the role of the Purkinje cell and where is it located?
The Purkinje cell is located in the cortex of the cerebellum of the brain and is fundamental in controlling motor movement. It is a multipolar neuron (lots of dendrites)
How is the nervous system broken down and classified?
- Central nervous system - brain & spinal chord
- Peripheral nervous system - everything else
How is the peripheral nervous system broken down further and classified?
- Somatic nervous system - controls all body movements (purposeful movement and reflexes) via skeletal muscles (efferent) and also transmits sensory information from the periphery to the CNS (afferent)
- Autonomic nervous system - controls organs and glands
How is the autonomic nervous system broken down further and classified?
- Parasympathetic nervous system
- Sympathetic nervous system
Which part of the brain is the somatic nervous system involved with in relation to controlled movement?
The brain receives somatosensory input (vast amount, not just pin prick - includes visual, where your limbs are in space) in the right somatosensory cortex (located in the parietal lobe) and this information is integrated in the many integration centres in the brain. The left motor cortex initiates action, sending messages to the somatosensory neurons to control the actions.
What are the roles of the parasympathetic and sympathetic nervous system?
- Parasympathetic - normal bodily functioning
- Sympathetic - ready for action / 'fight or flight' responses
- Remember: parasympathetic and sympathetic nervous systems are part of the autonomic nervous system which is part of the peripheral nervous system.
In the orientation of the brain, what is the front called?
Front of the brain is referred to as rostral / anterior to the rear of the brain
In the orientation of the brain, what is the rear called?
- Rear of the brain is referred to as caudal / posterior of the brain (towards the back)
- e.g. you might slice a brain caudally
In the orientation of the brain, what is the top called?
Dorsal / superior (heading towards the top)
In the orientation of the brain, what is the bottom called?
Ventral / inferior (heading to the bottom)
When slicing up the brain in neuroanatomy, what is the machine used, called?
Freezing microtome or cryostat
What are the three types of sectioning or slicing in neuroanatomy?
- Sagittal slice - slice from front to back (mid-saggital slice is a slice right down the middle from front to back)
- Coronal slice - 90 degrees to the sagittal - most common in animal research
- Axial / horizontal slice - horizontal plane across the brain
What are the bumps and crevices in the brain called?
- Gyrus - lump/ridge on the cerebral cortex
- Sulcus - depression in the cerebral cortex
- Fissure - deep sulcus in cerebral cortex
- White matter - made up of axons - white appearance due to myelin
- Cerebral cortex - grey matter made up of cell bodies
How are the brains of mammals similar/different?
Similar midbrain/hindbrain but differ greatly in forebrain
The hindbrain (cerebellum)/midbrain provides basic output and functioning to the periphery. The forebrain (cerebrum) is about higher order processing (learning and cognitive functioning)
What are the three sections of the brain?
- Hindbrain ('rhombencephalon') - control of vital functions (blood pressure, heart rate) - attached to spinal chord
- Midbrain ('mesencephalon') - relay station between forebrain and hindbrain
- Forebrain - controls everything else such as homeostatic functioning (keeping body temperature within normal range and maintaining fluid balance)
What are the two sections of the forebrain?
Diencephalon (thalamus) and telencephalon (creates cerebral cortex where higher order processing occurs)
Starting from rostral and heading caudal, where do the three sections of the brain sit?
- Rostral end you have forebrain (telencephalon first then diencephalon (thalamus) second), then midbrain (mesencephalon) then at the caudal of the brain you have the hindbrain (rhombencephalon)
What is the hindbrain made up of?
Where is the medulla and what is the medulla involved in?
It is located in the hindbrain and involved in autonomic functioning so is the centre for controlling heart rate and blood pressure. It is also a major input centre of cranial nerves
What happens if the medulla is damaged?
In most animals, the animal will not be compatible with life and most likely die.
Where is the pons and what is it involved in?
Pons is located in the hindbrain and it has three main functions: relays signals between periphery and higher levels of the brain such as the forebrain; respiration; and integration of cranial nerve activity
Where is the cerebellum and what is it involved in?
The cerebellum is located in the hindbrain and is primarily helps with fine motor control.
What happens when the cerebellum is damaged?
As the cerebellum is involved in fine motor control, if it is damaged, people suffer from cerebellum ataxia affecting coordinated muscle movement. Damage to the right side of the cerebellum affects right side of body and left side of cerebellum affects left side of body. However, left side of the brain controls right side of body (damage to left side of the brain can weak or paralyse right side of the body)
What is the midbrain composed of?
Where is the tectum located and what is it composed of?
Tectum is located in the midbrain and is composed of the superior colliculus (visual) and the inferior colliculus (auditory).
Where is the tegmentum located and what is its role?
Tegmentum is located just below the tectum in the midbrain. It is primarily involved in unconscious processes and the state of being conscious.
What happens if there are lesions in the midbrain?
Usually tend not to be compatible with life, particularly if the tegmentum is damaged.
What is the forebrain composed of?
- Hypothalamus (sits just below the thalamus)
- ThalamusAmygdalaHippocampusCerebral cortex / cerebrum
What is the function of the hypothalamus?
- Together with the pituitary gland, it is involved in hormone production
- Also important for homeostasis - lesions can cause overeating or not eating at all, or may remove ability to maintain body temperature
What is the function of the thalamus?
- Relay for sensory signals within the brain
- It also acts as a filter, preventing info that it does not need to be passed on
What is the function of the amygdala?
- Control of emotionsInvolvement in memory
What is the function of the hippocampus?
Generates and stores new memory especially episodic memories (events/experiences)
What can happen if the hippocampus is damaged/removed?
May lead to anterograde amnesia (unable to form new memories - episodic memories) and possibly partial retrograde amnesia (can't remember things before the event). Working and procedural memories are unaffected by damage to the hippocampus.
What are the four lobes of the cerebral cortex / cerebrum?
Going clockwise from frontal lobe, what is the order of the other lobes?
Frontal lobe, parietal lobe, occipital lobe and temporal lobe.
What separates the frontal lobe from the parietal lobe?
What separates the frontal lobe from the temporal lobe?
What is the role of the frontal lobe?
- Executive functioning - abstract thinking/problem solving
- Also involved in impulse control and related social skills
What is at the back of the frontal lobe?
Motor cortex which is mapped to different parts of the body. The association motor cortex (integration of info) sits in front of the primary motor cortex
What is the role of the parietal lobe?
Somatosensory intepretation - each part of the lobe is mapped to a different part of the body
How is the brain's plasticity demonstrated in the frontal and parietal lobe?
Frontal lobe contains the motor cortex and parietal lobe contains the somatosensory cortex. Each is mapped to different parts of the body. If you have a finger amputated, the brain remaps so takes up more space for the remaining fingers.
What is the role of the temporal lobe?
Auditory and olfactory processing. We don't have an olfactory cortex but we do have a primary auditory cortex.
How are the two halves of the brain connected?
Through the corpus callosum, which acts as a bridge. It is made up of white matter (white due to myelin sheath) and allows for rapid communication between the two hemispheres.
What is a synapse?
It is where neurons meet (synaptic cleft)
What are the two different types of synapses?
- Electrical (gap junctions) - faster than chemical signals but less common
- Chemical - slower than electrical and more complex connection but is the most common type of connection between neurons - chemical synapses can be graded
What are the signals travelling down the dendrites and cell body of the neuron called?
Chemical signals are translated into electrical signals (graded potentials)
What are the signals travelling down the neuron / axon called?
Action potential / nerve impulse is the transmission of rapid electrical signals down the neuron / axon
Describe the synaptic communication process.
- 1. Action potential / nerve impulse travels down axon to the axon terminal2. This positively electrically charged event leads to voltage gated calcium channels opening ('voltage gated' as they open in response to voltage change; here, voltage increases) and positive calcium is attracted into the negatively charged cell, so floods in.
- 3. Increased levels of calcium activate synaptic vesicles which contain neurotransmitters (neurotransmitters are the chemical signals between cells) which are released into the synaptic cleft4. Newly released neurotransmitter in synaptic cleft is free to potentially bind to the receptors on the postsynaptic cleft5. When neurotransmitter binds to receptor, a ligand-gated ion channel opens such that sodium is allowed in (increasing positive charge of cell - EPSP) and other neurotransmitters open up chloride channels (reduces charge of cell when they enter cell - IPSP)
- 6. Change in positivity and negativitiy is known as a post-synaptic potential or graded potential
What generally happens when neurotransmitters are released into the synaptic cleft?
Some of it gets degraded by enzymes but generally they are returned to the presynaptic neuron (neurotransmitter reuptake)
What are the different forms of synaptic communication?
- Axodendritic - axon leading to dendrite
- Axosomatic - axon signalling to cell body or soma
- Axoaxonic - synapse occurring between axon and axon
What is IPSP and EPSP?
- Both are graded potentnials and are potentials which move down the dendrites and cell body which are essentially summed together at the axon hillock
- IPSP - decreases in voltage called inhibitory post-synaptic potentials (chloride ion)
- EPSP - increases in voltage called excitatory post-synaptic potentials (sodium ion)
When will an action potential fire?
- When the EPSP (increase in voltage) exceeds the threshold. There is no such thing as a larger magnitude action potential or smaller magnitude action potential: an action potential either fires or not depending on the threshold.
What is the phospholipid bilayer made up of?
- Phospholipid - phosphate group attached to lipids (lipids are hydrophobic)
- Bilayer - there are two sides
What space does the phospholipid bilayer separate?
- Separates the extracellular space (space outside the cell which is positive due to having more sodium ions than inside) from the intracellular space (space inside cell - negative)
- Cell membrane is negatively charged and has a resting potential of -70 mV
What is the Nernst equation?
It helps determine how ions want to interact with the cell - pretty much works out the equilibrium potential for an ion
What is sodium's equilibrium potential and what does it tell you about its movement tendency
It has an equilibrium potential of +55 mV which is very different to the cells' resting potential (-70 mV) so it really wants to get into the cell
What is potassium's equilibrium potential?
K+ has an equilibrium potential of -90 mV, close to the cell's resting potential (-70 mV)
Say the threshold for a cell is -55 mV, how much must the membrane potential be raised up to in order for an action potential to fire?
The stimulus must raise the membrane potential up to 55 mV.
What is the sub-threshold EPSP?
The sub-threshold excitatory postsynaptic potential is the excitatory postsynaptic potential (increase in voltage) that doesn't quite reach the threshold for the cell so no action potential is fired at all.
What kind of channels run all the way down the axon of the neuron?
Voltage-gated sodium channels - they are 'voltage-gated' so they only open when the membrane reaches the threshold (for example, up to 55 mV)
Why might the cell only reach the sub-threshold EPSP?
The voltage-gated sodium channels only open up briefly then close up. When they close up, they cannot open again i.e. refractory
What is it called when the voltage-gated sodium channels are open?
When they are open, the cell membrane potential goes up as the sodium ions flood into the cell. This is called de-polarization of the membrane
What does potassium do when sodium floods into the cell?
When sodium floods into the cell and de-polarizes the membrane, potassium with an equilibrium potential of -90 mV isn't happy that the cell is +40 mV (for example, sub-threshold EPSP), so it repolarizes the cell and potassium floods out of the cell. After repolarization, potassium channels stay open
What are the three primary criteria for a neurotransmitter?
- Chemical or substance must be present within the presynaptic neuron
- Neurotransmitter/substance must be released in response to presynaptic depolarization (increase in voltage) and release must be Ca2+ dependent
- Specific receptors for the substance must be present on the postsynaptic cell
What are neuromodulators?
Many neurotransmitters act as neuromodulators where they travel around and also affect activity of other cells.
What are examples of neuromodulators?
- Cholinergic system
What are the two types of receptors?
- Ionotropic - when neurotransmitter binds to receptor, it opens and allows ions to enter
- Metabotropic (g-protein coupled receptors) - metobotropic is not about moving ions, but creating internal cascades - when activated, releases g-protein (intracellular messengers)
What are some features of the intracellular messenger?
- They signal within the cellThey are slower and longer acting than a ligand-gated channel
What are the types of neurotransmitters?
- Amino acid neurotransmitters
- Cholinergic neurotransmission (only one neurotransmitter involved)
- Monoamine neurotransmitters
- Peptide neurotransmitters (made up of many amino acids - involved in important behavioural functions)
What are the two types of amino acid neurotransmitters?
- Glutamate - primary excitatory neurotransmitter - 50% synapses release glutamate
- Gamma-aminobutyric acid (GABA) - primary inhibitory neurotransmitter
What is glutamate?
- An amino acid neurotransmitter
- There are metabotropic receptors and 3 types of ionotropic receptors (AMPA, Kainate, NMDA)
What is AMPA, Kainate, and NMDA?
- They are ionotropic receptors of glutamate. AMPA and Kainate allow sodium to flow into the cell and involved in generating excitatory post-synaptic potentials.
- NMDA creates neuroplasticity (change in brain) and highly important in learning. It's still ligand-gated but also allows calcium into the cell.
What is an example of an amino acid neurotransmitter?
GABA - primary inhibitory neutrotransmitter
What is the proportion of synapses using GABA neurotransmitter?
Around 25-40% of synapses are GABA
What are the different types of GABA receptors
- GABAA which is ionotropic (multiple binding sites and in the middle it has a chloride ion channel - when GABA is bound at binding site, chloride channel opens and let's chloride into the cell)
- GABAB which is metabotropic (less interesting for behavioural functioning)
What substance is involved in cholinergic neurotransmission
What are the two major classes of acetylcholine receptors in cholinergic neurotransmission
- Nicotinic acetylcholine receptors (ionotropic)
- Muscarinic acetylcholine receptors (metabotropic)
How is acetylcholine involved in the periphery?
- It controls a lot of the nerves - nerves coming out from the spinal chord are usually acetylcholine connections - acetylcholine neurotransmission is the transmission system for the somatic nervous system
- Motor neurons are acetylcholine neurons
How is acetylcholine involved in the autonomic nervous system?
- It is a major component of the autonomic nervous systemA lot of synapses controlling the autonomic nervous system (sympathetic or parasympathetic) are acetylcholine connections which can act on other neurotransmitters.
- Adrenaline act on acetylcholine receptors to activate sweat glands in terms of the sympathetic nervous system.
How is acetylcholine important within the brain?
- Within the central nervous system, the forebrain cholinergic system is associated with cognitive functioning.
- 4/5 of the approved drugs used to treat the effect (not cure) of Alzheimer's disease, act on the cholinergic system by inhibiting the breakdown of acetylcholine so that there is more acetylcholine around
What kind of receptor does acetylcholine act as in the central nervous system/cognitive functioning?
- Acetylcholine has two kind of receptors (nicotinic and muscarinic)
- In the CNS, they act as nicotinic receptors to improve reaction time.
Why are nicotinic receptors called that way?
Nicotine binds to these receptors, to improve reaction time.
What is the effect of being chronically exposed to nicotine on the nicotinic receptors?
Following chronic exposure to nicotine, it down-regulates the number of nicotinic receptors.
What are some subcategories of the monoamine neurotransmitters?
- Catecholamine neurotransmitters
- Serotonin (5-HT)
What do catecholamine neurotransmitter include?
Dopamine and epinephrine / norepinephrine (same as adrenaline / noradrenaline)
What kind of receptor is dopamine?
G-protein coupled receptor so are metabotropic
Where are receptors D1-D5 found?
Within the VTA (ventral tegmental area) and substantia nigra
What is the difference in projections between the reward and movement system of dopamine?
- Reward - from VTA to nucleus accumbensMovement - from substantia nigra to striatum
What did the experiment looking at dopamine and reward involved?
Olds and Milner injected current into the brains of rats. When they injected current in the medial forebrain (including hypothalamus), animals would like that that stimulation and they found that rats would self-stimulate this area of the brain. Stimulation provided dopamine release.
What happens when you block dopamine receptors
If you block dopamine receptors you normalize behaviour - you don't have the urge to self-stimulate forever.
What disorder is related to the dopamine neurons originating from the substantia nigra?
Dopamine from the substantia nigra are involved in movement of the body and so is related to Parkinson's disease - caused by destruction of dopamine producing cells and diminished substantia nigra.
What is a primary treatment for Parkinson's disease?
L-Dopa is the primary line of treatment for Parkinson's. It provides extra dopamine into the brain to continue movement functioning.
What is norepinephrine?
It is a subclass of catecholamine neurotransmitter which belongs to the monoamine neurotransmitters.
Where does the norepinephrine come from?
The locus ceruleus
What kind of receptors are norepinephrine?
Alpha and beta receptors but all are g-protein coupled receptors (metabotropic)
Which nervous system is norepinephrine involved in?
- It is a major hormone as well as neurotransmitter associated with the sympathetic nervous system activation (stimulate cardiac tissue and muscle).
- It is also a stress hormone
- Within the CNS, norepinephrine is responsible for concentration (fight-or-flight response as a stress hormone)
What is serotonin?
It is a type of monoamine neurotransmitter.
What disorder is serotonin primarily associated with?
Mood disorders - particularly major depressive disorder (MDD).
How does the drug, Prozac, work on serotonin?
It blocks serotonin reuptake, so that you have more serotonin in the cleft.
How can you suppress appetite using serotonin?
You can suppress appetite by blocking the reuptake of serotonin.
What are histamines?
They are a type of monoamine neurotransmitter
What are histamines used for in treatment?
Anti-histamines are a major class of allergy treatments, acting on metabtropic receptors.
What else is histamine involved?
- Sleep-wake cycle
- Histamine neurons are continuously firing during our waking hours. This drops down by 75% during slow wave sleep, and stops during REM sleep
What are the neuropeptides that you need to remember?
- Neuropeptide Y
Why are endorphins named the way they are?
They are endogenous (from within the body) activators from the same endogenous pathway as morphine
What kind of receptor do endorphins act as?
G protein-coupled receptors
What are the primary functions of endorphins?
- Block pain
- Induce pleasure within CNS
How does endorphins block pain?
Pituitary releases endorphins to act within autonomic nervous system to inhibit pain signalling broadly across the body. In the somatic nervous system, endorphins inhibit sensory pain signalling.
What is oxytocin?
- A type of neuropeptideOxytocin also known as the 'love hormone'
What happens when you inhibit the oxytocin system
It results in anti-social behaviour
What is neuropeptide Y?
- A type of neuropeptideA major signalling hormone in terms of appetite
What happens when you inject an animal's brain with neuropeptide Y (NPY)?
- They will start eating.
- Elevated NPY leads to overeating and obese phenotype
What happens if you remove neuropeptide receptors from an animal's brain?
The 'NPY knockout animal' will not get fat even if on a high-fat diet.
What is psychopharmacology about?
The effect of drugs on the brain and behaviour
What is an agonist and antagonist?
- Agonist - chemical that binds to a receptor, and activates that receptor to enhance cellular activity
- Antagonist - binds to a receptor, but prevent agonist-mediated effects so blocks cellular activity
What is an enzyme inhibitor
Enzymes break down neurotransmitters. Enzyme inhibitors prevent this activity so that there are more neurotransmitters available
What is the difference between pharmacodynamics and pharmacokinetics
- Pharmacodynamics - physiological effects of drugs
- Pharmacokinetics - what the body does on the drug (metabolises it, excretion)
What are the different routes of drug administration (injection methods)
- Intravenous injection (IV) - into the vein (rapid absorption)
- Intraperitoneal injection (IP) - into the gut, getting into blood stream quickly (animal research usually)
- Subcutaneous injection (SC) under the skin (insulation injection for diabetics - takes longer to get absorbed)
- Intramuscular injection (IM) - into the muscle
Others include: inhalation (into lungs), topical (absorbed through skin), oral (via mouth)
What happens when you repeatedly use drugs?
- Tolerance - diminished drug effect or requires increased dosage to maintain constant effect
- Withdrawal - when you do not take drug after becoming tolerant, withdrawal effects often opposite to drug effect
- Sensitization - less common effect but where you become more sensitive than before using the drug
What was the initial class of antidepressants used to treat depression?
- The monoamine oxidase inhibitor prevents the breakdown of monoamine neurotransmitters.
- Monoamine neurotransmitters include dopamine, norepinephrine and serotonin (and histamine).
- That means there is increased levels of serotonin, dopamine and norepinephrine.
- Problem is that they have poor side-effects - can't take other drugs or interfere with different foods - also poor cardiovascular side-effects from lots of adrenaline.
What was the next class of antidepressants developed in the late 1950s?
- Tricyclic antidepressants inhibit the reuptake of serotonin (5-HT) and norepinephrine (NE)
- So you have more norepinephrine and serotonin in the synaptic cleft - so more 5-HT and NE signalling.
What was the antidepressants developed in the 1980s?
- Selective serotonin reuptake inhibitors (SSRIs) - inhibited the reuptake of just serotonin
- End up with more serotonin in the synaptic cleft
- SSRIs take weeks to work
What are antipsychotics?
- Typical antipsychotics, known as neuroleptics, treated the positive symptoms of schizophrenia (e.g. hallucinations).
- Block or antagonize the D2 receptors by binding to D1 receptors and not letting dopamine bind as much so you have a reduction in dopamine signalling
- Extrapyramidal side effects (EPS) including Parkinsonian symptoms (problems with movement)
What were the next antipsychotics to be developed?
- In the 1990s, atypical antipsychotics were developed
- Antagonized both D2 and 5-HT2 (serotonin 2) receptors
- Better side-effect profiles and similar effectiveness
- Don't bind to receptors as tightly as the older antipsychotics and don't affect dopamine transmission as much
- Newer antipsychotics are believed to contribute to weight gain
What is the difference between anxiolytics and depressants?
- Anxiolytics - reduce anxiety
- Depressants - sedatives (sleep-inducing) or narcotics (change mood)
What was the first class of drugs to bind on the GABA receptor to treat anxiety as an anxiolytic?
The barbiturates because it bound to the barbiturate site of the GABA receptor (GABA has lots of binding sites) - these drugs had unfavourable side-effects - if you overdose, you could fall into a coma and die.
What was the next class of drugs developed in the 50s that bound to the GABA receptor?
- Benzodiazepines used as anxiolytics to reduce anxiety
- Increases GABA's effect but doesn't open up chloride channels as the barbiturates did
- It is difficult to overdose on benzodiazepine
What else are benzodiazepines used as besides being an anxiolytic agent?
- Sedatives and hypnotics (treat insomnia e.g. temazapam)
- Anticonvulsant (treatment of epilepsy)
- Muscle relaxant
What is the best known depressant?
- Alcohol - acts through GABA signalling
- GABA is the major inhibitor of neurotransmission
Why do we initially feel a high from ingesting alcohol?
It increases dopamine and endorphine levels.
What are opiates and opioids?
Opiates and opioids are not strictly depressants but are more accurately analgesic or narcotic drugs.
What is the difference between opiates and opioids?
- Opiates - natural sources (opium poppy)
- Opioids are made in the lab (synthetic and semi-synthetic)
What is opium poppy therapeutically used for?
- For the treatment of acute pain
- However, commonly abused - dependence is common as tolerance happens very quickly - severe withdrawal symptoms arise if you abruptly discontinue use
What activators do opiates and opioids act on?
Opiates and opioids act on exogenous activators of the endorphine system
What are euphoriants?
Drugs that induce the feeling of euphoria (cocaine, amphetamine, marijuana)
What happens when euphoriants are abused?
It reduces brain metabolism of glucose uptake
What is the difference between neural communication and endocrine/hormonal communication?
- Neural communication involves sending nerve impulses from cell to cell to a specific target response - fast signalling - digitised messages (either all or none)
- Endocrine / hormonal communication - send info from blood stream to target tissues around the body - analogue message (little or a lot of hormonal secretion)
What is a condition for cells to be affected by hormones?
There must be a receptor protein that recognises the hormone
Hormone levels vary throughout the day: what are the relative levels of melatonin, cortisol and growth hormone?
- Melatonin - huge increases at night (associated with biological rhythm) when eye is not getting light
- Cortisol - peak in morning and coincide with meals/snacks (released when stressed and when you eat)
- Growth hormone - spike after bedtime
What are the different types of hormones?
- Peptide (peptide neurotransmitters are usually peptide hormones but not always) - string of amino acids
- Steroid hormones derived from cholesterol (a fat)
- Amine hormones composed of a single amino acid and modified into a molecule to act as a hormone
How are peptide hormones produced?
- Peptide hormones refer to a short string and protein hormones refer to a long string of amino acids.
- They are produced via the genetic system - DNA is transcribed into messenger RNA and that is translated into protein.
- Oxytocin is a neuropeptide neurotransmitter and also a peptide hormone and is produced in the hypothalamus.
What are steroid hormones produced from and where?
From cholesterol and produced in the gonads and adrenal glands, released by diffusion from the cell.
How are amine hormones produced?
They are derived from amino acids and not generated genetically, but usually by our diet. Enzymes convert the amino acids from our diet into these hormones.
How are peptide hormones and amine hormones released?
While both are produced differently, they are released similarly in being packaged into secretory vesicles and released by exocytosis from the cell membrane into the circulation.
What are the potential types of stressors?
- Acute stressful events are a focal event such as public speaking or being chased by a huge dog
- Chronic stressful events are the daily hassles of life (work, study, relationships)
What do stressors activate?
They activate the HPA-axis and sympathetic nervous system to varying degrees. Despite different types of stresses we face, similar physiological effects are apparent.
What happens when the HPA axis is activated?
Hypothalamus releases CRH (corticotropin-releasing hormone) then pituitary releases ACTH (adrenocorticotropic hormone) which leads to adrenal release of corticosteroids.
What kind of stress is the HPA-axis and sympathetic nervous system better able to respond to?
Acute stresses rather than chronic stresses. For chronic stress, they are maladaptive.
What are the two mechanisms that achieve homeostasis?
- Negative feedback (afferent & efferent signals)
- Anticipatory responses (behavioural)