Chapter 4, The Chemistry of Behaviour Flashcards
What does Neurochemistry focus on?
The basic chemical composition and processes of the nervous system
What is Neuropharmacology?
The study of compounds that selectively affect the nervous system.
What is Neurochemistry?
The branch of neuroscience is concerned with the fundamental chemical composition and processes of the nervous system.
What is Exogenous?
Arising from outside the body.
Explain the versatility of Neurotransmitters.
May activate ionotropic receptors at some synapses.
- Different NT for different subtypes of receptor
- 14 subtypes for serotonin, 5 for Dopamine, 5 for Norepinephrine
May activate a metabotropic receptor at another synapse.
What is an Ionotropic Receptor?
Also called a Ligand-gated ion channel and chemically gated ion channel. A receptor protein includes an ion channel that is open when the receptor is bound by an agonist.
What is a Metabotropic Receptor?
A receptor protein that does not contain an ion channel but may, when activated, use a G-protein second-messenger system to alter the functioning of the postsynaptic cell.
What is a Receptor?
Also called receptor molecule. A protein that binds and reacts to molecules of a neurotransmitter or hormone.
What are the criteria for Neurotransmitters in the Presynaptic cell?
- Substance exists in presynaptic axon terminals
- Is synthesized in presynaptic cells
- Is released when action potentials reach axon terminals.
What are the criteria for Neurotransmitters in the Postsynaptic cell?
- Receptors for the substance exist on the postsynaptic membrane.
- When experimentally applied, the substance produces changes in postsynaptic cells
- Blocking substance release prevents changes in the postsynaptic cell
What are the types of Neurotransmitters (NT)?
- Amine NT = Acetylcholine, Dopamine, Serotonin, epinephrine, norepinephrine, melatonin
- Amino Acid NT = Gamma-aminobutyric acid (GABA), Glutamate, aspartate,
- Peptide NT (or neuropeptides) = Short-chain amino acids
- Gas NT = Soluble gases; nitric oxide, carbon dioxide.
What is Co-localization (co-release)?
Occurs when nerve cells contain more than one type of neurotransmitter.
A Neurotransmitter is what for a particular receptor?
An endogenous ligand
What is the name of a drug that can bind to a receptor and activate it?
A receptor agonist
Can drugs also act as agonists?
Yes, if they block reuptake or degradation of a Neurotransmitter.
What is the name of a drug that can bind to a receptor but does not activate it?
A receptor antagonist
What can Receptor Antagonists be?
It can be competitive (when they bind to the same site as the endogenous ligand)
Or they can be non-competitive or neuromodulators (when they bind to an alternate site and prevent the receptor from activating).
Can drugs interfere with synaptic transmission?
Yes, drugs can interfere with the many different processes involved in synaptic transmission.
What is Glutamate?
It is a major excitatory NT in the CNS.
- Most of the activity in the brain results from glutamate signaling.
- There are ionotropic and metabotropic glutamate receptors.
- To terminate glutamatergic synaptic transmission, glutamate is taken up by neighboring astrocytes.
What is GABA?
A major inhibitory NT in the CNS.
-Inhibition plays a very important role in brain function. GABA signaling is responsible for many of the IPSP’s generated in the brain.
What is Glutamatergic?
Referring to cells that use Glutamate as their synaptic transmitter.
What is Excitotoxicity?
The property by which neurons die when overstimulated, as with large amounts of Glutamate.
What are some of the Ionotropic Glutamate receptors?
- AMPA
- NMDA
- Kainate
The binding of glutamate to ionotropic receptors results in what?
The opening of a sodium ion channel.
Activation of the Metabotropic Glutamate receptors can be either what?
- Excitatory
- Inhibitory
What are the Gamma-aminobutyric (GABA) receptors divided into?
- GABA(A)—ionotropic, producing fast, inhibitory effects
- GABA(B)—metabotropic, slow inhibitory effects
- GABA(C)—ionotropic with a chloride channel
What GABA agonist is a potent tranquilizer?
Valium
What is Phencyclidine (PCP)?
It is an NMDA receptor antagonist. Originally developed as an anesthetic, PCP is considered a dissociative hallucinogen as it produces feelings of depersonalization and detachment from reality.
What is Ketamine (Special K)?
It is a less potent NMDA antagonist that has similar effects to PCP.
How do you terminate Gamma-amn=inobutyruc (GABA)?
To terminate GABA synaptic transmission, GABA is taken up by neighboring astrocytes.
What are the kinds of GABA receptors?
- Ionotropic
- Metabotropic
What are GABA(A) receptors?
They are receptors that are ionotropic, and activation of a GABAA receptor results in the opening of a chloride ion (Cl-) channel. This causes hyperpolarization of the postsynaptic cell (IPSP).
What interacts with GABA(A) receptors?
- Benzodiazepines (like Valium), barbiturates, and alcohol all interact with the GABAA receptor and potentiate (enhance) the effects of GABA. (GABA receptor agonists)
- These drugs are all anxiolytics, meaning they can reduce feelings of anxiety.
How was Acetylcholine (ACh) mapped?
By the enzymes involved in its synthesis
What is Acetylcholine (ACh)?
A neurotransmitter produced and released by parasympathetic postganglionic neurons, by motor neurons, and by neurons throughout the brain
Where is Acetylcholine (ACh) present?
- The PNS, including all neuron to muscle synapses (neuromuscular junctions) and in both divisions of the ANS.
- Present in many regions of the CNS including the basal forebrain and regions within the hindbrain.
What Cholinergic?
Referring to cells that use Acetylcholine as their synaptic transmitter.
Cholinergic nerve cell bodies and projections contain ACh.
- Lost in Alzheimer’s disease
- Involved with learning and memory
What degrades (ACh) and where?
Acetylcholinesterase (AChE) degrades ACh in the synaptic cleft.
What can (ACh) be divided into?
- Nicotinic receptors
- Muscarinic receptors
What are Nicotinic receptors?
Referring to cholinergic receptors that respond to nicotine as well as to acetylcholine.
- There are many different nicotinic receptors
- Nicotinic receptors are ionotropic.
- Initially named “nicotinic” because (many of) these receptors are sensitive to nicotine
What are Muscarinic receptors?
Referring to cholinergic receptors that respond to the chemical muscarine as well as to acetylcholine.
- There are many different muscarinic receptors
- Muscarinic receptors are metabotropic
- Initially named muscarinic because these receptors are sensitive to muscarine
What are the roles of Acetylcholine?
- ACh is important for all muscle contractions.
- ACh is important for the function of the sympathetic and parasympathetic divisions of the ANS
- ACh in the CNS is associated with attention, cognition, and memory.
Cholinergic cells degenerate in what disease?
Alzheimer’s disease.
What are the symptoms of Alzheimer’s disease?
The symptoms of Alzheimer’s disease (including memory loss and dementia) are thought to result from the loss of cholinergic neurons in the brain.
This suggests that ACh signaling normally supports memory formation and cognition.
What are Acetylcholine Agonists?
- Nicotine
- Sarin
What is Nicotine?
It is a nicotinic acetylcholine receptor (nAChR) agonist – nicotine is a stimulant, it can enhance cognitive functions (like attention and memory), and increase feelings of pleasure.
Nicotine is also rewarding and reinforcing, making it addictive.
What is Sarin?
It is a synthetic AChE inhibitor – used as a chemical weapon.
Causes convulsions, over-activation of the ANS, suffocation, and death.
What are Acetylcholine Antagonists?
- Curare
- Scopolamine
What is Curare?
nAChR antagonist - causes paralysis, used in hunting
What is Scopolamine?
mAChR antagonist – can impair cognitive functions (like attention and memory formation)
What drugs act on the Cholinergic System?
- Sarin
- Scopolamine
- Curare
- Nicotine
What are the two main classes of Monoamines?
- Catecholamines—dopamine, epinephrine, norepinephrine
- Indoleamines—melatonin, serotonin
In Dopamine (DA) Anatomy what are the two primary dopaminergic pathways?
- Mesolimbocortical Pathway
- Mesostriatal Pathway
What is the Mesolimbocortical Pathway
Neurons in the midbrain project to areas in the limbic system and cortex
What is the Mesostriatal Pathway
Neurons in the substantia nigra (midbrain) project to the striatum (caudate and putamen of the basal ganglia)
Are there multiple receptors for Dopamine and how is synaptic transmission terminated?
There are multiple Dopamine receptors (D1-D5), and all are metabotropic. Synaptic transmission is terminated by reuptake of Dopamine through Dopamine transporters.
What are the roles of Dopamine (DA)?
Important for voluntary movement (mesostriatal pathway)
Important for reward, reinforcement, and addiction (mesolimbocortical pathway)
Implicated in schizophrenia (mesolimbocortical pathway)
Which dopamine pathway is implicated in Schizophrenia?
Mesolimbocortical pathway is Implicated in schizophrenia
- Dopamine hypothesis of schizophrenia
- Over-activity of dopaminergic neurons
Associated with positive symptoms
-Hallucinations, delusions, and disorganized thinking.
What is Dopamines’s role in Parkinson’s Disease?
- The dopaminergic neurons of the substantia nigra produce less DA and ultimately die
- leads to a host of predominantly motor symptoms including weakness, resting tremors, and a mask-like face
What are some Dopamine Agonists?
- Cocaine (stimulant)
- Amphetamine (stimulant)
What does cocaine do as a Dopamine Agonist?
- Blocks the DA reuptake transporter
- can trigger feelings of enhanced energy, well-being, and self-confidence. It creates a sense of euphoria making it rewarding and reinforcing, and also addicting.
What does Amphetamine do as a Dopamine Agonist?
- It causes increased DA release (through a reversal of the DA reuptake transporter)
- It causes increased energy, reduced appetite, and increased wakefulness. It also causes a sense of euphoria and is therefore reinforcing, and addicting.
What do First Generation Antischizophrenic drugs do?
Block Dopamine receptors
-e.g. haloperidol
What is Catecholamine?
A class of monoamines that serve as neurotransmitters, including dopamine and norepinephrine.
What is Indoleamine?
A class of monoamines, including serotonin and melatonin, serves as neurotransmitters.
What is the Striatum?
The caudate nucleus and putamen together.
What is the ventral tegmental area (VTA)?
A portion of the midbrain that projects dopaminergic fibers to the nucleus accumbens.
What is a Serotonergic?
Referring to neurons that use serotonin as their synaptic transmitter.
What is the Raphe Nuclei?
A string of nuclei in the midbrain of the midbrain and brainstem that contain most of the serotonergic neurons of the brain.
What is the connection between Dopamine and rewards?
Most rewards activate the dopaminergic neurons in the ventral tegmental area causing increased dopamine release into various structures of the frontal lobe.
Where is Serotonin (5HT) mostly found?
In the raphe nuclei, and their serotonergic fibers project widely.
What is Serotonin (5HT) implicated in?
It is implicated in sleep, mood, sexual behavior, anxiety, appetite, and aggression.
What drugs increase Serotonin (5HT) activity?
Antidepressants, such as Prozac, increase Serotonin activity and the effects depend on which receptor subtypes are affected.
What does (5HT) mean?
5-Hydroxytryptamine
What is the synaptic transmission of Serotonin?
It consists of multiple Serotonin receptors, with most being metabotropic. Degradation controls overall levels of (5-HT) with the enzymes that degrade serotonin being called MonoAmine Oxidases (MAOs). Synaptic transmission is terminated by reuptake of Serotonin transporters.
What are some Serotonin Agonists?
- LSD
- Psilocybin
- MDMA
- Antidepressants (MAO inhibitors, SSRIs, etc.) block (5HT) transporters
What are LSD and Psilocybin?
They are serotonin receptor agonists (at 5-HT2A receptors), both these drugs are hallucinogens (drugs that alter sensory perceptions).
These drugs tend to distort visual perceptions, but other effects are possible.
What is MDMA?
It is Ecstacy, and it increases 5-HT and DA levels (possibly through the reversal of the transporters).
This leads to both stimulant and hallucinogenic effects.
What is some information on LSD?
- Activates many subtypes of monoamine receptors (DA, 5-HT)
- Results in heightened activity in frontal, cingulate, and occipital cortex
- Perceptual changes
- An altered sense of time, novel visual objects, intense colors in geometric patterns
- Alcoholism, addictions, anxiety
What is some more information on Psilocybin?
- Partial agonist
- Particularly those in the visual cortex
- Modifies activity of the frontal and occipital cortex
- Spiritual experiences and feelings of transcendence
- Intense visual experiences and altered perception of time
- Treatment of OCD, migraines, anxiety
What is Norepinephrine?
A compound that acts as both an NT produced and released by the sympathetic postganglionic neurons to accelerate organ activity, and as a hormone released from the adrenal medulla under the control of the sympathetic nervous system, which prepares the body for action.
What is Epinephrine?
it is Adrenaline, and it is synthesized from norepinephrine. Made mainly in the adrenal medulla (above the kidneys) and is only released in times of stress.
What are Norepinephrine and Epinephrine synthesized from?
Dopamine
What does an insufficient or ineffective use of Norepinephrine (NE) cause?
ADHD, Depression, and Hypotension (low blood pressure)
What medications agonists increase Norepinephrine (NE)
Adderall, Amphetamines, and Ritalin
What are high levels of Norepinephrine associated with?
High levels of NE are associated with anxiety disorders, chronic stress, Bipolar disorder (mania), high blood pressure
What are Clonidine and Beta-blockers?
Norepinephrine antagonists
What do neuropeptides called endorphins (and enkephalins and dynorphins) bind to?
They bind to opioid receptors in the brain. These molecules are part of our endogenous pain control system.
What are some Opioid Agonists?
Drugs like morphine (codeine, heroin, fentanyl, and oxycodone) also bind to the opioid receptors and act as agonists.
How do the types of opioids and the routes of administration affect the behavior effects of these drugs?
Faster routes of administration (such as intravenous heroin, or inhaled opium) can lead to feelings of euphoria. In addition, opioids are used to treat pain and diarrhea, and as a cough suppressant.
What does Naloxone do?
Naloxone or Narcan (competitive opioid antagonist) binds to opioid receptors
What is Gas Neurotransmitters and how is it different than a typical NT?
Nitric Oxide (NO) is a Gas NT -Laughing gas
Different action than typical NT
-Produced in locations other than axon terminals (dendrites)
- Diffuse from neuron rather than being released
- Doesn’t bind to receptors – diffuses into the target cell
- Act as retrograde transmitters - diffuses from the postsynaptic cell back to presynaptic cell and stimulates the production of second messengers
What is Gas NT important for?
- Blood vessel health (lowers blood pressure)
- Changes synaptic efficacy involved in learning and memory
- Hair growth
- Penile erection (used to treat erectile dysfunction)
How does alcohol affect the body?
- effects are biphasic—an initial stimulant phase followed by a depressant phase.
- Alcohol activates GABA(A) receptors and increases inhibitory effects; contributes to social disinhibition and loss of motor coordination.
- Also stimulates dopamine pathways, causing euphoric effects.
What are the adverse effects of Alcohol?
- Alcohol abuse damages nerve cells; the frontal lobes are most affected, yet some effects are reversible.
- Korsakoff’s Syndrome
- Periodic overconsumption, or bingeing, may cause brain damage and reduces neurogenesis.
- Fetal alcohol syndrome is the result of pregnant women abusing alcohol, with permanent damage to the fetus.
What is Anandamide (the bliss molecule)?
An Endocannabinoids
Anandamide is what and affects us how?
Anandamide is one of the endogenous ligands that activate the CB receptors.
- Alters memory formation
- Stimulates appetite
- Reduces pain sensitivity
- Protects from excitotoxic brain
- damage
- Lowers blood pressure
- Combats nausea
- Lowers eye pressure from glaucoma
Delta9-Tetrahydrocannabinol (THC) is what?
It is CB receptor agonist. Cannabinoids have many effects such as relaxation, disinhibition, increased hunger, and possibly reduce pain.
What Is Bioavailability?
The degree to which a drug or other substance becomes available to the target tissue after administration.
In oral administration how does a drug travel?
Gut (Absorbed in the small intestine) -> blood (through walls of the intestine into the bloodstream then directed to the liver first before brain) -> brain
In Inhalation administration how does a drug travel?
Lungs -> blood (directed to the heart than the brain) -> brain
What is a Tolerance?
Successive drug treatments with a particular drug result in decreasing effects. There are two main types of tolerance:
- Metabolic tolerance
- Functional tolerance
What is Metabolic Tolerance?
The body becomes more effective at clearing the drug.
What is Functional Tolerance?
Decreased response to a drug often resulting from up-or down-regulation of drug receptors. The target tissue may show altered sensitivity to the drug.
What is Cross-tolerance?
When the tolerance to one drug generalizes to other similar-type drugs
What is Withdrawal?
Unpleasant symptoms that occur when a person stops using a drug
What factors affect vulnerability to drug abuse?
Many factors figure in an individual’s susceptibility to addiction:
- Biological—sex, genetic predisposition
- Family situation—family breakup, poor relationships, sibling drug users
- Personal characteristics—aggressiveness, emotional control
- Environmental factors—peer pressure, social factors
What is cue-induced drug use?
Is the increased likelihood of using a drug because factors are present that were also present when the drug was last used.
What do Medications to treat drug abuse do?
- Lessen the discomfort of withdrawal and drug craving
- Provide alternatives to the addictive drug
- Block the action of the addictive drug
- Alter metabolism of the drug
- Block the brain’s reward system
- Vaccines may be effective in reducing the drug’s reward and preventing addiction.
What two main clusters is Norepinephrine released from into the brainstem?
- Locus Coeruleus (pons)
- Lateral Tegmental System (Midbrain)
There are four subtypes of (NE) receptors and they are all what?
Metabotropic
What do the (NE) systems modulate?
The (NE) systems modulate processes including mood, arousal, and sexual behavior.
What are the two types of Cannabinoid receptors (which both are G-protein coupled metabotropic receptors)?
- CB(1) receptors are only found in the CNS and mediate the rewarding properties of cannabinoids.
- CB(2) receptors are prominent in the immune system.
Where are Cannabinoid receptors most concentrated?
The receptors exist throughout the body and brain but are more highly concentrated in the substantia nigra, the hippocampus, the cerebellar cortex, and the cerebral cortex.
What is Binding Affinity?
The degree of chemical attraction between a ligand and a receptor
- Neurotransmitters – low-affinity ligands
- High-affinity drug: selectively binds to a type of receptor (even at low doses) and stays bound for a longer time
- Low-affinity drug: the same dose will bind to fewer receptors
Affinity determines what?
Efficacy of a drug and its efficacy (or intrinsic activity) is the ability of a bound ligand to activate the receptor.
What is a Partial Agonist?
It produces a medium response regardless of dose. So when the combination of affinity and efficacy determines the action of the drug
What has high and low efficacy?
- Agonists have high efficacy
- Antagonists have low efficacy.
So when the combination of affinity and efficacy determines the action of the drug
What is a Dose-response curve (DRC)?
It is a graph of the relationship between drug doses and the effects.
The DRC is a tool to understand pharmacodynamic—the functional relationship between drugs and their targets.
What is the Therapeutic Index?
It is the separation between an effective dose and a toxic one.
What is an ED(50)
The Effective does 50%
How can the drug potency of two drugs be compared?
By their ED(50)
And drugs that have comparable effects at lower doses is more potent
Neurons Down-regulate in response to what?
Agonist Drugs - fewer receptors available and becomes less sensitive and countering drug effects
Neurons Up-regulate in response to what?
Antagonist drugs - increase the number of receptors and becomes more sensitive
What is Catecholamine?
A class of monoamines that serve as neurotransmitters, including dopamine and norepinephrine.
What is Indoleamine?
A class of monoamines, including serotonin and melatonin, serves as neurotransmitters.
Who discovered Acetylcholine (ACh)?
Otto Loewi
