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Chapter 4


What is a neurochemical (+ additional criteria)? A substance released by one cell that produce a reaction in a target cell, and is... 1. Present within a presynaptic cell 2. Released in response to presynaptic depolarization 3. Interacts with specific receptors on a postsynaptic cell
What are the categories of neurochemicals? Neurotransmitters, neuromodulators and neurohormones
How do neurotransmitters operate; What is the difference between this action and neuromodulators and neurohormones? Neurotransmitters participate in directed synapses by acting on neurons in their own immediate vicinity at a synapse. Neuromodulators and neurohormones participate in non-directed synapses by acting on more distant neurons.
What is ""volume transmission""? " The process in which neuromodulators diffuse away from their site of release. So-called because large volumes of the nervous system can be influenced.
Why are neuromodulators able to continue to influence the activity of the central nervous system? They remain in the cerebrospinal fluid for extended periods of time.
How do neurohormones operate? They travel in the blood supply, and interact only with other cells that have specialised receptor sites
What are the classes of neurochemicals? Small molecules, neuropeptodes and gasotrasmitters
What are the subgroups of small molecules? Acetylcholine (ACh), Monoamines, Amino Acids and ATP and its byproducts
What are the subgroups of Monoamines? Cathecholamines and Indoleamines
Where are small molecules and neuropeptides synthesised? Small molecules are synthesised in the axon terminal, and neuropeptides are synthesised in the cell body and must be transported (can take up to one day)
What happens to vesicles used by small molecules and neuropeptides? Vesicles used by small molecules can be recycled, but vesicles used by neuropeptides are used only once.
What is the difference between the release of small molecules and neuropeptides? Neuropeptides require higher levels of calcium and thus higher rate of action potentials
What is the difference between the deactivation of neuropeptides and small molecules? Neuropeptides cannot be deactivated by reuptake
How are chemical messengers used by neurons? Many neurons release a small molecule along with a neuropeptide, and a neuron can release two small molecules in different locations
What do motor neurons release? They release acetylcholine onto muscle fibers and other neurons in the spinal cord but release glutamate only in the spinal cord.
How is acetylcholine (ACh) synthesised? Choline acetyltransferase (ChAT) acts on choline and acetyl coenzyme A to produce ACh.
What are the sources of Acetyl Coenzyme A (acetyl CoA) and choline, the two precursors to ACh? Acetyl CoA comes from metabolic activities of mitochondria, and choline comes from dietary fats and breakdown of existing ACh.
What is ChAT and why is it a useful idicator for identifying cholinergic neurons? ChAT is choline transferase and it is found only in neurons that produce ACh
What is the function of acetylcholinesterase (AChE)? It breaks down any ACh in the synaptic gap, producing Choline which is then recaptured and resythesized
Where is ACh used? It is the primary neurotransmitter at the neuromuscular junction, and is essential in the Autonomic nervous system: all preganglionic synapses and postganglionic synapses in the parasympathetic division are cholinergic.
Where are cholinergic neurons in the brain; What do they do? Major groupings are located in the basal forebrain, septal area, and brainstem. They influence the cerebral cortex, hippocampus and amygdala. They appear to participate in attention, wakefulness, learning and memory.
What are the subtypes of cholinergic receptors? Nicotinic receptors and muscarinic receptors. They are named after the substances they react to other than ACh.
What is the difference between nicotinic and muscarinic receptors, in terms of structure? Nicotinic receptors are ionotropic receptors, while muscarinic receptors are metabotropic receptors.
Where are the nicotinic and muscarinic receptors located? Nicotinic receptors are found at the neuromuscular junction, while muscarinic receptors are located in heart muscles and other smooth muscles. The CNS contains both receptors; muscarinic is more abundant. They are also located in the autonomic NS.
What are monoamines broken down by? In the axon terminal, they are broken down by monoamine oxidase (MAO). Outside neurons, cathecholamines (and not indoleamines) are broken down by cathechol-O-methyl-transferase (COMT).
How are various cathecholamines synthesized? 1. Tyrosine hydroxylase (TH) that acts on tyrosine 2. The enzyme dopa decarboxylase then acts on L-dopa 3. (DBH) then acts on dopamine 4. Norepinephrine is then released back into the intracellular fluid, acted upon by (PNMT) 5. Epinephrine
What is the function of dopamine systems; What diseases are they associated with? Dopamine systems are involved with motivated behaviours and the processing of reward e.g. addiction. They are suspected of playing a role in schizophrenia and attention deficit hyperactivity disorder (ADHD)
Where are cells releasing dopamine located? They are located in the midbrain and form connections with other parts of the brain along several major pathways.
What are the dopamine pathways? The first pathway is the mesostriatal/nigrostriatal pathway. The second pathway is the mesolimbocortical system. There are also two other pathways in the hypothalamus: the paraventricular dopamine system and the hypothalamic dopaminergic pathway.
Where does the mesostriatal/nigrostriatal pathway originate; What are its two parts, and where do they go; What are their functions? Substantia nigra. First part: up to caudate nucleus, putamen and global pallidus in basal ganglia. Second part: down to the nucleus accumbens, olfactory cortex, caudate nucleus, and putamen. Function: Voluntary motor activity, reward and incentive.
What are the parts of the mesolimbocortical system; What is its function? Ventral tegmentum in midbrain, projects to parts of the limbic system and cortex. Connections bet. midbrain and limbic system motivated behaviour, connections bet. the midbrain and cortex participate in higher-level cognitive functioning
What are the parts of the paraventricular dopamine system; What does it do? It connects the hypothalamus to the thalamus and to sympathetic neurons in the spinal cord. It coordinates motivated behaviour e.g. sex.
What are the parts of the second hypothalamic dopaminergic pathway and what does it do? It connects to the pituitary gland and controls milk production in mammals.
What are the two classes of dopamine receptors; What are the similarities and differences between the two classes i.e. what do they do and where are they located? 1st is D1 and D5, 2nd is D2, D3 and D4. All metabotropic receptors. 1st excitation while 2nd inhibition. All in basal ganglia but: 1st can also be found in hippocampus and hypothalamus, 2nd can also be found in frontal lobes, thalamus and the brain stem.
What are epinephrine and norepinephrine also referred to as? Adrenaline and noradrenaline.
What is epinephrine; Where can it be found, and what does it do? It is an important neurohormone. It can be found in cells in two areas in the medulla. It coordiates eating and regulates blood pressure.
"What is an ""adrenaline rush"" in biological terms? " It is the result of the release of epinephrine from the adrenal glands located above the kidneys into the blood supply.
Where can norepinephrine be found; Where is its most important source? Neurons that secrete norepinephrine can be found in the pons, medulla, and hypothalamus. Its most important source is the locus coereleus of the pons.
What is special about the locus coeruleus? Although it might contain as little as 4000 neurons that secrete norepinephrine, these neurons have axons with as many as 100000 collaterals each. These project to the spinal cord and nearly every major part of the brain.
What are the functions of the norepinephrine circuits? Activity in these circuits increase arousal and vigilance
Where can norepinephrine be found in the nervous system? It can be found in the peripheral nervous system at the postganglionic synapses of the sympathetic division, where it is involved in arousal.
What are the receptor types that respond to either norepinephrine or epinephrine; Where can they be found? They are called alpha or beta receptors respectively, and are all metabotropic. They can be found in the central nervous system and target organs that respond to the sympathetic division activity and neurohormones.
How is serotonin synthesised? 1. Tryptophan is obtained from dietary sources (grains, meat and dairy products). The enzyme Tryptophan hydroxylase acts on tryptophan 2. 5-hydroxytryptophan (5-HTP) is obtained. 5-HTP decarboxylase then acts on 5-HTP 3. Serotonin is obtained.
How many serotonergic neurons are there; Where are they located? There might be as few as 200000 in the human brain. Some can be found in the medulla and cerebellum, but most are located in the raphe nuclei of the brainstem.
Where do serotonergic neurons project to; What types of synapses are formed? They project to the spinal cord, the cerebellum, the limbic system and the cerebral cortex. The more rostral neurons form direct synapses, while those in the medulla form indirect synapses.
How many subtypes of serotonergic receptors are there; What type of receptor are they? There are nearly 15 that have been identified, and all but one are metabotropic.
What does serotonin do? It regulates sleep, mood, social status, appetite and aggression. Low levels are associated with depression, lower social rank, increased risk taking and aggression.
How is histamine synthesized; What subtypes of receptors are there, and what does it do? It is synthesized from the action of histidine decarboxylase on histidine in the presence of vitamin B6. It is correlated with wakefulness: Antihistamines are used to treat insomnia and allergies.
How many types of amino acids are there, and what are the three most important ones? There are as many as 8 that function as chemical messengers. The three important ones are glutamate, gamma-aminobutyric acid (GABA) and glycerine. Glutamate and glycerine are used to build other proteins (amongst 20 other basic amino acids).
How is glutamate synthesised; What does it do? It is synthesized from alpha-ketoglutarate in the mitochondria. It is the most common excitatory neurochemical in the CNS.
Why must the synaptic area be cleared of excess glutamate? Excess glutamate action can be toxic: adverse reactions include chest pain, headache, nausea and rapid heartbeat.
What are the three major types of glutamate receptors; What type of receptor are they? N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), and kainate. AMPA and kainate are both ionotropic: they operate a sodium channel and produce EPSPs. NMDA is metabotropic.
Why is the NMDA receptor special in two ways? 1. both voltage-dependent and ligand-dependent: glutamate must be present and the postsynaptic membrane must be depolarized at the same time for it to open. 2. allows both positively charged sodium and calcium ions to enter the cell - hyperpolarisation
How does the NMDA receptor work? 1. At resting potential, ion channels of NMDA receptors are blocked by magnesium ions. 2. AMPA receptor located nearby opens, allows sodium nearby to move through the receptor - depolarization, kicking the magnesium ion. 3. Glutamate binds, receptor opens
What does the NMDA receptor do? It may participate in functions such as long-term memory. However, too much glutamate can digest and kill the affected neurons due to the action of calcium upon entering the cell, as might happens in strokes.
How is GABA synthesized; What does it do? It is synthesied from glutamate through the action of the enzyme glutamic acid decarboxylase (GAD). It is the major inhibitory neurochemical of the CNS.
What type of GABA receptors are there; How do they operate? There are the GABAA and GABAB receptors. GABAA is a ionotropic postsynaptic chloride channel that allows chloride ions to enter the cell (as when it interacts with psychoactive substances). GABAB is a metabotropic potassium channel - potassium leaves cell
How is glycine synthesized; What does it do; What does its receptors do? enzyme serine transhydroxymethylase acts on serine in mitochondria. acts directed syapses as inhibitory neurochemical, acts as an excitatory neurochemical with glutamate at NMDA. Manages sleep-waking cycles. Receptors allow chlorine to enter cell
What is adenosine triphosphate (ATP) and its byproducts; What do they do? They act as neurochemicals in the CNS and in connections between autonomic neurons and the vas deferens, bladder, heart and gut. ATP is involved with the perception of pain and sleep-wakig cycles. Adenosine (byproducts) inhibits release of other chemicals
Outline the properties of neuropeptides in relation to neurons and receptors as well as deactivation. There are at least 40 different ones that act as neuromodulators and neurohormones. A single neuron can produce many different neuropeptides, and often c
What are some important neuropeptides? Substance P is involved in the perception of pain. Endogenous morphines (endorphins) are a class of neuropeptides that act on the same receptors as opioids. Peptides involved with digestion such as insulin and cholecystokinin (CCK), as well as peptide
What are gasotransmitters; What are the more important gasotransmitters? They are gases that transport information from one cell to another. Some examples are nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S).
How is nitric oxide synthesized; What does it do? It is synthesized by actions of the ezyme nitric oxide synthase (NOS) found in onnly 1-2 percent of neurons in the cerebral cortex, on the amino acid arginine. It is involved with neural communications, the maintenance of blood pressure and erections.
Why are gasotransmitters unique? They diffuse through membranes without needing vesicles or a release mechanism. They act on receptors within cells, and are able to travel through cells. They break down very quickly without needing enzymes. They also appear to transfer information fr
What are agonists and antagonists? Agonists are drugs that enhance the activity of a neurochemical. Antagonists are drugs that reduce the activity of the neurochemical.
How do agonists and antagonists work vis a vis production of neurochemicals; What are some examples? Agonists increase the production of neurochemicals e.g. eating high carbohydrate meals, resulting in larger amount of tryptophan synthesized into serotonin. Antagonists decrease the production of neurochemicals e.g. the drug alpha-methyl-p-tyrosin
How do antagonists work vis a vis neurochemical storage? They work by interfering with the storage of neurochemicals in vesicles within the neuron e.g. reserpine which interferes with the uptake of monoamines such as serotonin, resultig in abnormally small quantities being released
How do agonists and antagonists work vis a vis exocytosis; What are some examples? Exocytosis is promoted by agonists but blocked by antagonists. Methamphetamine, a dopamie agonist, displaces dopamine in the vesicles. This higher concentration of dopamine in the intracellular fluid causes transports to reverse and pump dopamine
How do agonists and antagonists work vis a vis receptor sites; What are some examples? Agonists are similar enough in chemical composition to mimic the action of natural neurochemicals at the receptor site. Antagonists block synaptic activity by occupying a binding site on a receptor without activating the receptor. Nicotine and muscari
How do antagonists such as benzodiazepines, alcohol and barbiturates work at the GABAA receptor? They are GABA agonists, which enhance the inhibiting effect of GABA. Barbiturates ca single handedly activate the GABAA receptor, while the others need to bind as the same time GABA is present. There are 5 other binding sites on the GABAA receptor, as
How do agonists work vis a vis reuptake and enzymatic degradation; What are some examples? Agonists inhibit reuptake or enzymatic degradation, thus allowing more of the released substance to stay active in the synapse and interact with receptors. Fluoxetine (Prozac) does this with serotonin, cocaine, amphetamine and methylpheidate (Ritalin)
What causes tolerance to drugs? Changes in enzymes, increased receptor density, learning and classical conditioning.
What is addiction? Compulsive need to use a drug repeatedly in spite of negative consequences to the user.
What are the psychological mechanisms of addiction? Changes in the brain's reward system overwhelm the impulse control system managed by the frontal lobe. This is caused by the more intense and longer-lasting dopamine release caused by addictive drugs. In addition, a craving system involving th
How is addiction treated by medication in heroin addicts and alchoholics; How do vaccinations work vis a vis addiction? Methadone is used to wean away heroin addicts: it has the added benefits of preventing withdrawal symptoms without producing the psychological effects of heroin. Disulfuram interferes with ALDH which metabolizes alcohol, producing unpleasant symptoms
What are psychoactive drugs; What are some examples of psychoactive drugs? They are drugs administered to obtain a particular psychological effect, and circumvent the blood-brain barrier to access the CNS. Caffeine, nicotine, cocaine and amphetamine, Ecstasy (MDMA), Opioids, Marijuana, LSD, Alcohol are all psychoactive drugs.
What does caffeine do; How does it work; What are its positive and negative effects? It increases blood pressure and heart rate, improves concentration, and wards off sleepiness. It works by blocking adenosine receptors, reducing its inhibitory activity in the hippocampus, cerebral cortex and basal ganglia. It has the benefit of prote
What does nicotine do; How does it operate; What are its downsides? "It increases heart rate and blood pressure, promotes the release of adrealine into the circulation, reduces fatigue and heightens cognitive performance. In the PNS, it also produces muscular relaxation. It is an agonist at the nicotinic cholinergic rece
" Cocaine and amphetamie are both powerful dopamine agonists. How do they work; What do they do? Coke: Dopamine reuptake inhibitor. Amphetamine: stimulates both dopamine and norepinephrine release and inhibits both reuptake. At high doses, produce schizophrenia-like symptoms. Long-term amphetamine use leads to extesive neural damage.
How does Ecstasy (MDMA) operate; What does it do? It reduces the function of serotonergic neurons. It also stimulates the release of serotonin and oxycontin .This produces increased sociability. It also increases heart rate, blood pressure and body temperature for between 3 to 6 hours.
What is an opioid; What is an opiate; What does it do? ... A substance that interacts with endorphin receptors. An opiate is a substance derived from the sap of the opium poppy e.g. morphine (precursor of heroin) and codeine. Opiates are used in pain management, cough suppression and diarrhea treatment.
What are opioids' effects? At low doses, they produce euphoria, pain relief, lack of anxiety, muscle relaxation, and sleep. At much higher doses, they depress respiration, which may lead to death.
From an evolutionary perspective, what is the purpose of endorphins? They allow us to escape emergency situation in spite of extreme pain.
Why are opiates addictive? They increase dopamine activity as they bind to endorphin receptors.
What are the effects of marijuana (smoked cannabis)? They cause either some excitation and mild euphoria, or depression and social withdrawal. At higher doses, they produce hallucination.
Cannabis contains over 50 psychoactive compounds, or cannabinoids. What do they do? They are implicated in pain, learning, appetite and movement.
What is THC; How does it work? It is tetrahydrocanabinol, a psychoactive compound (cannabinoid) in cannabis. It acts as an agonist at receptors for endogeous cannabinoids (endorphins are a close equivalent), which is how THC produces some of its behavioural effects.
What types of cannabinoid receptors are there; Where are they located? They are CB1 and CB2. They interact with endogenous cannabinoids anadamide and sn-2 arachidonylglycerol (2-AG). CB1 receptors can be found in the basal ganglia, cerebellum, and cerebral cortex, but most numerous in the hippocampus and prefrontal cortex.
Why does THC have negative effects on memory formation? Cannabinoid receptors are present in the hippocampus and prefrontal cortex. It might inhibit glutamate release, adversely influencing hippocampal activity and memory.
What is LSD; How does it operate? It is lysergic acid diethylamid (LSD). It acts as a serotonergic agonist in the cerebral cortex.
What are the effects of LSD? It can cause flashbacks, intrusive and unwanted hallucinations even after quitting the drug. It may also produce long-term changes in brain function which are not yet understood.
What does alcohol do at low, high and very high doses? Low doses - dilates blood vessels. providing a warm, flushed feeling -It reduces anxiety, promotes assertiveness, reduces behavioral inhibitions. At higher doses, aggression, risky behaviour. Motor coordination drops. At very high doses, coma and death.
How does alcohol produce its effects? Agonist at the GABAA receptor - neural inhibition. It also stimulates dopaminergic pathways: euphoric and addictive qualities. Antagonist at the NMDA glutamate receptor, causing memory problems. It also acts on endorphin receptors as well.
Why does alcohol produce rapid tolerance? It increases production of liver enzymes that eliminate alcohol from the system. It also causes changes in receptor number and characteristics e.g. GABAA and NMDA.
What are the effects of alcohol withdrawal syndrome? Sweating, nausea and vomiting, sleeplessness and anxiety. Hallucinations and dangerous seizures can also occur.
What are the bad effects of alcohol? Damages parts of the brain - frontal lobes. Indirectly cause Korsakoff's sydrome, worse ability to form new memories. Lack of Vitamin B1 damage hippocampus. Raise risk of breast cancer for genetically vulnerable women. complications in fetus development.
What is the one good effect of alcohol? Light to moderate alcohol consumption can reduce risk of heart disease.
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