Chapter 4: The Chemistry of Behavior - Neurotransmitters and Neuropharmacology

Flashcard set covering Chapter 4 lecture materials on neurochemistry, neurotransmitter pathways, receptor subtypes, neuropharmacology, dose-response relationships, and drug mechanisms.

What is neurochemistry?

The study of the basic chemical composition and processes of the nervous system.

What is neuropharmacology?

The study of compounds that selectively affect the nervous system.

What does co-localization (or co-transmission) mean in neuroscience?

The phenomenon where a single neuron contains and releases more than one type of neurotransmitter.

What are the six classic criteria used to define a substance as a neurotransmitter?

1. Exists in presynaptic axon terminals; 2. Synthesized in presynaptic cells; 3. Released when action potentials reach terminals; 4. Receptors exist on the postsynaptic membrane; 5. Experimental application produces postsynaptic changes; 6. Blocking release prevents these postsynaptic changes.

What are the four main chemical families of neurotransmitters?

Amino acid neurotransmitters, amine neurotransmitters, peptide neurotransmitters (neuropeptides), and gasotransmitters.

Which neurotransmitters are classified as amino acid neurotransmitters?

Gamma-aminobutyric acid (GABA), glutamate, glycine, and histamine.

What is the most prevalent excitatory neurotransmitter in the brain?

Glutamate.

What are the three ionotropic receptor subtypes for glutamate?

AMPA, kainate, and NMDA receptors.

What function are NMDA glutamate receptors especially implicated in?

Learning and memory.

What is the most prevalent inhibitory neurotransmitter in the brain?

Gamma-aminobutyric acid (GABA).

How do GABAA and GABAB receptors differ in their mechanism?

GABAA receptors are ionotropic (fast inhibitory channels), while GABAB receptors are metabotropic.

How do GABA agonists like Valium affect the central nervous system?

They act as potent tranquilizers by enhancing GABA's inhibitory signaling, reducing neural excitability.

What was the first neurotransmitter to be identified?

Acetylcholine (ACh).

Where are the primary clusters of cholinergic cell bodies located in the brain?

In the basal forebrain (including the nucleus basalis, medial septal nucleus, and nucleus of diagonal band).

Which neurodegenerative disease is characterized by a major loss of cholinergic neurons?

Alzheimer's disease.

Which neurotransmitter system and pathways are depicted in this brain diagram?

The cholinergic system, originating in the basal forebrain nuclei and brainstem (pedunculopontine/laterodorsal tegmental nuclei) and projecting to the cortex, hippocampus, and cerebellum.

What are the key features of nicotinic acetylcholine receptors?

They are ionotropic, fast-acting, excitatory, and used at neuromuscular junctions to trigger muscle contraction.

What happens when nicotinic ACh receptors are blocked by an antagonist such as curare?

Muscle paralysis.

What are muscarinic acetylcholine receptors, and what drugs block them?

They are metabotropic (G protein-coupled) receptors that can be excitatory or inhibitory; they are blocked by atropine or scopolamine.

Which neurotransmitters are classified as catecholamines, and what amino acid are they derived from?

Dopamine (DA), epinephrine (adrenaline), and norepinephrine (NE), all derived from tyrosine.

Which neurotransmitters are classified as indoleamines, and what amino acid are they derived from?

Serotonin (5-HT) and melatonin, derived from tryptophan.

What is the mesostriatal dopamine pathway, and what disease is associated with loss of its neurons?

A motor-control pathway originating in the substantia nigra and projecting to the striatum (caudate and putamen); death of these neurons causes Parkinson's disease.

What is the origin, projections, and function of the mesolimbocortical dopamine pathway?

It originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens, limbic system, cortex (including insula), and hippocampus; it is involved in reward and reinforcement.

Which neurotransmitter system and pathways are shown in this diagram?

The dopaminergic pathways: the mesostriatal pathway (substantia nigra to striatum) and the mesolimbocortical pathway (VTA to nucleus accumbens, cortex, and hippocampus).

From which two main brainstem regions is norepinephrine released?

The locus coeruleus and the lateral tegmental area.

Which pathway system in the brain is illustrated in this diagram?

The noradrenergic pathway, originating in the locus coeruleus and lateral tegmental area.

Where are serotonin (5-HT) cell bodies primarily located in the brain?

In the raphe nuclei of the brainstem.

Which neurotransmitter pathways originating from the raphe nuclei are shown here?

The serotonergic pathways.

How do selective serotonin reuptake inhibitors (SSRIs) increase serotonin activity?

By blocking the reuptake transporter that clears 5-HT from the synaptic cleft back into the presynaptic terminal.

How does nitric oxide (NO) differ from classical neurotransmitters?

It is produced in dendrites (not axon terminals), diffuses immediately without vesicle storage, has no membrane-bound receptors, and acts as a retrograde transmitter by diffusing into presynaptic cells.

Which serotonin receptor subtype is ionotropic and specifically involved in nausea?

The 5-HT3 receptor.

What is an agonist drug?

A drug that binds to a receptor and activates it, mimicking the action of an endogenous ligand.

What is an antagonist drug?

A drug that binds to a receptor without activating it, blocking endogenous ligands from binding and activating the receptor.

How does a noncompetitive ligand (neuromodulator) differ from a competitive ligand?

It binds to a distinct regulatory site on the receptor rather than competing directly with the endogenous neurotransmitter for its binding site.

What concept regarding neurotransmitter action is demonstrated in this illustration?

A single neurotransmitter can directly open an ionotropic ligand-gated channel at one synapse or activate a metabotropic G protein-coupled receptor at another.

What is binding affinity?

The degree of chemical attraction between a ligand and a receptor.

How do endogenous neurotransmitters compare to high-affinity drugs regarding binding duration?

Endogenous neurotransmitters are low-affinity ligands, allowing them to dissociate rapidly, whereas high-affinity drugs stay bound to receptors longer.

According to this diagram, how does drug affinity affect the concentration required to bind half the receptors?

A low-affinity drug requires a higher concentration to bind half the receptors, whereas a high-affinity drug requires a lower concentration.

What is drug efficacy (or intrinsic activity)?

The ability of a bound ligand to activate the receptor and produce a biological response.

What is a partial agonist?

A drug that produces a moderate, submaximal response regardless of how high a dose is administered.

What does ED50 represent on a dose-response curve?

The effective dose at which a drug produces 50% of its maximal response.

How is relative drug potency determined from dose-response curves?

By comparing ED50 values; the drug that produces comparable maximal effects at lower doses is more potent.

What is the therapeutic index of a drug?

The separation/difference between useful doses (ED50) and dangerous/lethal doses (LD50 or TD50).

Based on this graph, why is Lorazepam safer than Phenobarbital?

Lorazepam has a wide therapeutic index (a large separation between ED50 and LD50), whereas Phenobarbital has a narrow therapeutic index, making overdose much easier.

What is pharmacokinetics?

The study of factors that affect the movement of a drug into, through, and out of the body.

Which central injection route administers a drug directly into the cerebral ventricles to bypass the blood-brain barrier?

Intracerebroventricular injection.

Which peripheral injection method has the slowest effect and why?

Subcutaneous injection, because the drug must diffuse through nearby tissue before entering the bloodstream.

What is bioavailability?

The amount of administered drug that is free to act on its target tissue.

What is the difference between metabolic tolerance and functional tolerance?

Metabolic tolerance occurs when organ systems become more effective at clearing/eliminating the drug; functional tolerance occurs when target tissues alter their receptor sensitivity.

How do target cells alter receptor density in response to agonists versus antagonists?

Target cells downregulate (decrease) receptors in response to an agonist or repeated activation, and upregulate (increase) receptors in response to an antagonist.

What cellular process is shown in panel (A) versus panel (B) of this figure?

Panel (A) shows receptor downregulation in response to an agonist; Panel (B) shows receptor upregulation in response to an antagonist.

How does colchicine impair neurotransmitter production presynaptically?

It impairs the maintenance of microtubules, blocking axonal transport of materials needed for neurotransmitters.

How does reserpine affect presynaptic neurotransmitter storage?

It blocks the packaging of neurotransmitters into synaptic vesicles, leaving them vulnerable to breakdown by enzymes.

How does tetrodotoxin (TTX) prevent synaptic transmission?

It blocks voltage-gated Na+ channels, preventing action potential conduction down the axon.

How does verapamil alter presynaptic neurotransmitter release?

It blocks calcium channels, reducing the influx of Ca2+ ions that drive synaptic vesicle exocytosis.

How does caffeine act as a stimulant presynaptically?

It competes with adenosine for presynaptic receptors, preventing adenosine from exerting its normal inhibitory effects on transmitter release.

How does Botox (botulinum toxin) cause local muscle paralysis?

It disrupts vesicle-fusion proteins in motor neurons, preventing the release of acetylcholine (ACh).

What presynaptic mechanisms targeting transmitter clearance are summarized in section C of this diagram?

Inactivation of transmitter reuptake (e.g., cocaine, amphetamine, antidepressants) and blockade of transmitter degradation enzymes (e.g., MAO inhibitors).

How does haloperidol act postsynaptically as an antipsychotic drug?

It acts as a receptor antagonist that blocks dopamine D2 receptors.