PSB Exam 2

What are the seven steps of neurotransmitter function? Describe each of these steps.

1) Neurotransmitter synthesis: peptide neurotransmitters synthesized in DNA from soma. 2) Neurotransmitter storage: vesicular packaging in the golgi apparatus in soma or axon terminal. 3) Neurotransmitter release: action potentials cause vesicles to migrate toward presynaptic membrane and to fuse with the membrane. They also cause them to open and release NT. 4) Binding to autoreceptors: NT can bind to autoreceptors on presynaptic membranes to inhibit further synthesis and release. 5) Binding to postsynaptic receptors: receptors require usually 2 molecules of NT and are selective. 6) Neurotransmitter reuptake: released NT are reuptaken into presynaptic neuron by specialized transporter proteins like DAT, NET, SERT. 7) Enzymatic degradation: released NT are degraded by specific extracellular enzymes.

What is a drug? How can it get into the nervous system? Where do drugs exert their actions?

A drug is an exogenous chemical that is not an essential nutrient and significantly alters function of cells when taken in low doses. It can get into the nervous system through membrane receptors on cell membranes. Drugs exert their actions on molecules on/within cells.

How do affinity and efficacy contribute to the actions of a drug?

A drug with a high affinity for a particular receptor will selectively bind to that receptor even at low doses and for a long time. Low affinity drugs will bind fewer receptors and dissociate easier. Efficacy is the extent to which a drug activates a response when it binds to a receptor.

What are autoreceptors?

A receptor for a synaptic transmitter that is located in the presynaptic membrane, telling the axon terminal how much transmitter is released.

. What is a second messenger?

A slow acting substance in the postsynaptic cell that amplifies the effects of synaptic activity and signal synaptic activity within the postsynaptic cell.

Describe the synthesis, packaging, inactivation, and reuptake of acetylcholine.

ACh is synthesized by choline acetyltransferase ChAT from choline and acetyl CoA. It is packaged into vesicles by VAChT, inactivated by hydrolysis of ACh to its choline by AChesterase. It is reuptaken by high affinity choline transporter ChT and then converted back to ACh.

What are the possible routes of administration of a drug?

Absorption (oral, topical), injection and inhalation, as well as spinally or intracranially

Describe 7 mechanisms of agonist action and 7 mechanisms of antagonist action. Give some examples.

Agonist: drug is a precursor to a NT, stimulates NT release, blocks autoreceptors, activates postsynaptic receptors, blocks reuptake, inactivates metabolizing enzyme. Antagonist: inactivates biosynthetic enzyme to make NT, prevents NT storage, activates autoreceptors, inhibits NT release, blocks postsynaptic receptors.

Compare agonist and antagonist drugs.

Agonists mimic or increase neurotransmitter actions whereas antagonists block or decrease neurotransmitter actions. Agonists have high efficacy and antagonists have low efficacy

What is the incentive sensitization theory of drug addiction?

As drug craving increases, drug liking increases

What is the relative permeability of sodium, chloride and potassium at resting potential?

At resting potential, potassium is highly permeable whereas sodium and chloride are not.

What are the classical and atypical neuroleptic drugs? Where do they act?

Classical: haloperidol, chlorpromazine. Atypical: clozapine, risperidone. Antagonists are D2,3, and 4 receptors.

Describe competitive, noncompetitive, and irreversible antagonists.

Competitive, or direct, attach to the same binding site as the endogenous neurotransmitter. Noncompetitive, or indirect, bind to a noncompetitive site. Irreversible modify receptor making it permanently inactive.

Compare and contrast dependence, psychomotor stimulant, and opponent process theories of drug addiction.

Dependence says that addiction is defined by physical dependence and withdrawal symptoms. Psychomotor stimulants: a common denominator of addictive substances is their ability to induce psychomotor activation and activate dopaminergic receptors. The role of physical dependence is ascribed as a secondary role. Opponent process says that drug exposure initiates an adaptive process that opposes the hedonic effects of the drug, but persists are termination of the drug exposure, leading to more drug-taking behavior.

Name 3 catecholamines

Dopamine, norepinephrine and epinephrine

Distinguish drug sensitization from drug tolerance

Drug sensitization is an increase in effectiveness of a drug with repeated/chronic exposure. Drug tolerance is a decrease in the effectiveness of a drug with repeated/chronic exposure.

Which ions are responsible for the inward and outward currents during an action potential?

During an action potential, sodium rushes inward while potassium flows outward.

Describe the EPSP and IPSP and explain how neurotransmitter-dependent ion channels contribute to postsynaptic potentials.

EPSP is when the postsynaptic potential is depolarized and IPSP is when the postsynaptic potential is the potential is hyperpolarized, moved away from threshold. IPSPs normally result from the opening of Chloride channels, which causes a hyperpolarization of the cell. EPSPs occur from the opening of Sodium channels.

Describe the potential risks of ecstasy, opiates, and methamphetamine.

Ecstasy is known for impurities and can impair verbal reasoning, attention, mood, impulse control, can cause heart attacks. Meth can cause memory loss, aggression and violence, psychotic behavior. Opiates cause nausea, vomiting, respiratory depression, coma

Name the endogenous neurotransmitter system that marijuana (i.e., THC) emulates?

Either endocannabinoids or GABA?

Which neurotransmitter serves mostly as a hormone (secreted by the adrenal medulla) and has only limited function as neurotransmitter in the brain?

Epinephrine.

Describe the roles of executive function, genetic predisposition, and personality traits in drug addiction.

Executive function says that vulnerability for drug addiction is highest in adolescence because the frontal cortex (reasoning and judgement) develops slower than subcortical mechanisms (basic drives). Genetic predisposition to alcoholism exists. Personality traits include risk-taking behavior and stress hyper-responsivity.

Name 3 amino acid neurotransmitters

Glutamate, GABA, and glycine

Distinguish hyperpolarization and depolarization.

Hyperpolarization is when the membrane potential becomes more negative and depolarization is when the membrane potential becomes more positive.

What are the normal functions of acetylcholine in your nervous system?

Implicated in motor function (NMJs), REM sleep (pons), learning and memory (basal forebrain), addictive effects of nicotine

How do ventral and dorsal dopamine systems contribute to addiction?

In the ventral systems, nucleus accumbens helps acquire drug addiction. Dorsal striatum establishes drug-taking habits.

How are monoamine neurotransmitters subdivided?

Into catecholamines and indoleamines

Distinguish ionotropic and metabotropic receptors

Ionotropic receptors directly control ion channels. When bound by the transmitter, the ion channel opens and ions flow across the membrane. Also known as ligand-gated ion channels. Metabotropic receptors recognize synaptic transmitter but do not directly control ion channels. They activate G proteins.

What happens when a drug is broken down in your body?

It becomes broken down into biologically active molecules, converting into metabolites. These metabolites may have therapeutic, harmful, or negligible effects

What types of receptors does acetylcholine bind?

It binds ionotropic nicotinic receptors and metabotropic muscarinic receptors.

What is the Nernst equation?

It is a function that predicts the voltage needed to counterbalance the diffusion force pushing an ion across a semipermeable membrane.

Where is acetylcholine found in your nervous system?

It is found in preganglionic fibers of sympathetic and parasympathetic neurons, motor neurons, brainstem, basal forebrain (basal nucleus of Meynert) and in striatum

What is meant by the "all-or-none" principal?

It means that if the membrane potential does not reach threshold, the action potential will not fire, no matter how depolarized the membrane is. "All-or-none" refers to the fact that the amplitude of the action potential is constant no matter the magnitude of the stimulus.

Describe the mechanism by which the Na+-K+ pump works.

It pumps three sodium ions out for every two potassium in.

Describe the first experimental evidence that synapses use chemicals to communicate.

Leowi stimulated a frog vagus nerve (from the heart) in one bath that was connected to another bath, found that both hearts responded to the stimulus, even though they were only connected by water.

Name 2 indoleamines.

Melatonin and serotonin.

What is membrane permeability?

Membrane permeability refers to certain ions' ability to cross the cell's membrane. The membrane is selectively permeable, so only certain ions can cross it

glutamate

Most abundant excitatory NT. Synthesis from glucose metabolism. Located all over the brain, binds to AMPA, NMDA, kainate receptors (ionotropic). Implicated in sensory processing, plasticity, and virtually every brain function. Deficits in schizophrenia and epilepsy. NMDA and AMPA activate postsynaptic receptors. PCP and memantine (Namenda) block them.

GABA

Most abundant inhibitory NT. Synthesis from glucose metabolism. Inactivated by glial uptake. All over the brain. Binds to GABA receptors. Same implications and deficits as glutamate. Diazepam and EtOH activate postsynaptic receptors and bicucline blocks them.

Name one soluble gas neurotransmitter. How does it function?

NO causes rapid blood vessel dilation.

Why do we consider some drugs to be neuromodulators? Provide some examples of neuromodulatory actions.

Neuromodulators perform broader actions than do G-proteins. Neuromodulatory actions include presynaptic facilitation/inhibition: actions that increase or decrease release of NT; synaptic actions: actions to modulate actions of glutamate/GABA/glycine; extrasynaptic actions: actions on receptors outside synapse to modulate actions of glutamate/GABA/glycine

What is non-synaptic chemical communication?

Neurons have membrane-bound receptors, cytosolic and nuclear receptors which are non-synaptic and bind a variety of neurotransmitters. The non-synaptic membrane ones are mostly metabotropic and the other two are metabotropic.

What drugs interact with acetylcholine neurotransmission, and how?

Nicotine and muscarine activate postsynaptic receptors, curare blocks postsynaptic receptors, donepezil (Aricept) inactivate metabolizing enzyme

Reconstruct the action potential in terms of the movement of ions across the plasma membrane.

Open K+ channels create the resting potential. If membrane is depolarized to threshold, voltage-gated Na+ channels open, leading to a rapid depolarization—the action potential. The Na+ channels close automatically and gated K+ channels open, repolarizing and may hyperpolarize (afterpotential). All gated channels close and cell returns to resting potential.

opioid and non-opioid peptides

Opioid (endorphin, enkephalin, dynorphin). Non-opioid (peptide YY, substance P). Manufactured in soma, inactivated by diffusion or enzymatic metabolism. Opioids implicated in analgesia, socialization, feeding, behavior reinforcement. Bind to metabotropic receptors. Heroin, morphine, oxycodone activate postsynaptic receptors, naltrexone blocks them. Nonopioids are in regulation of feeding, gastric motility, circadian rhythms, mood disorders.

Describe treatment strategies for addiction to opiates, stimulants, nicotine, and alcohol. How effective are these strategies?

Opioid addiction: methadone (liquid administration). Used as maintenance, not a cure. Works slowly but reduces harm. High black-market value. Buprenorphine reduces craving for heroin. Stimulant addiction: bromocriptine promotes craving for coke and AMPH and produces dysphoria b/c it blocks DRs. Nicotine: Nicotine gum and patches maintain craving and help fight urge to smoke. Rimonobant has side effects but is quite successful. Alcohol: naltrexone makes alcohol less pleasurable and taste bad.

What is pharmacokinetics?

Pharmacokinetics is the process by which drugs are absorbed, distributed, metabolized, and excreted (ADME).

Distinguish ion pumps and ion channels.

Pumps are energetically expensive whereas channels are more passive

What is saltatory conduction?

Saltatory conduction refers to the form of conduction in which the action potential jumps from one node of Ranvier to the next.

How are psychoactive drugs classified? Give a general overview of each.

Sedative hypnotics and anxiolytics are minor tranquilizers and sleeping pills (alcohol, barbiturates and benzodiazepines). Antipsychotics relieve symptoms of schizophrenia (neuroleptics). Antidepressants increase extracellular serotonin. Narcotic analgesics like opium and heroin. Stimulants like coke and AMPH.

Describe the first experimental evidence that demonstrated that neurons exchange information through synapses.

Sherrington studied leg flexion reflex in dogs, found that reflexes are lower than conduction along an axon, meaning there must be gaps and delays at synapses. When one set of muscles is flexed, the other is relaxed, meaning an input can simultaneously excite outputs at some synapses and inhibit those at other synapses.

Describe the general distributions of chloride, sodium, and potassium ions in neurons (i.e., higher or lower on inside, etc.)

Sodium is generally higher in concentration outside of the cell, potassium is generally higher in concentration inside the cell, and chloride is generally higher outside the cell

What are spatial and temporal summation?

Spatial summation is when potentials are summed from different physical locations across the cell body. Temporal summation is when there are gaps in time between stimulations. These stimulations have effects that overlap, and the closer the overlap, the more complete is the summation.

What are synapses and where can they occur? (List and describe 6 types of synapses)

Synapses are gaps between neurons. Axodendritic synapses are axon to dendrite; axosomatic are axon to soma; axoaxonic are axon to axon. Dendritic synapses occur on some very small interneurons. Varicosities are beadlike swellings along axon where NT are released, may form synapse. Gap junctions or electrical synapses are ion channels directly between neurons. Type I synapses are excitatory and have thick postsynaptic density. Type II synapses are inhibitory and have a more symmetrical postsynaptic density.

glycine

Synthesis from glucose metabolism, predominant inhibitory NT in brainstem, spinal cord, retina. Binds to ionotropic glycine receptor. Strychnine (rat poison) and tetanus toxin block postsynaptic receptors

What are the 7 features of a classical neurotransmitter?

Synthesized by presynaptic neuron, released by presynaptic neuron when stimulated, can be chemically or pharmacologically identified, binds to specific receptors on postsynaptic membrane, should reproduce at postsynaptic cell effects that are observed upon stimulation of presynaptic neuron, binding to postsynaptic receptors prevents action potentials from affecting them, active mechanisms to terminate actions of chemical (neuronal or glial uptake, enzymatic degradation).

norepinephrine

Synthesized by tyrosine in post ganglionic fibers of sympathetic nervous system, cells that project from locus coeruleus. Inactivated by reuptake through NET. Binds to metabotropic receptors. Regulation of mood, arousal, sexual behavior, fight or flight, depression, schizophrenia. Deficiency suspected in alzheimer's. Adrenaline and ephedrine activate postsynaptic receptors. Ritalin blocks reuptake, clorgyline inactivates metabolizing enzyme, beta-blockers block postsynaptic receptors.

serotonin

Synthesized from tryptophan. Inactivated by SERT reuptake. Located in 9 raphe nuclei and released from varicosities. Bind to mostly metabotropic receptors. Implicated in mood, feeding, sleep, pain,arousal. Deficits in depression, bipolar disorder, OCD. LSD activates postsynaptic receptors, clozapine blocks them, SSRIs block reuptake

dopamine

Synthesized from tyrosine, inactivated by reuptake through DAT, or by MAO-A, MAO-B. Located in nigrostriatal and mesocorticolimbic neurons. Binds to metabotropic dopamine receptors. Implicated in movement, attention, learning, motivation. Deficits in Parkinson's, schizophrenia, and drug addiction. Interactions: L-DOPA is precursor, reserpine prevents storage, apomorphine activates autoreceptors, cocaine and AMPH block reuptake, apomorphine activates postsynaptic receptors. Neuroleptics block postsynaptic receptors, deprenyl inactivate metabolizing enzyme

How does the myelin sheath contribute to the propagation of an action potential down the axon?

The myelin sheath greatly speeds conduction.

How is an action potential conducted in an unmyelinated neuron?

The neuron has to be very large. Each portion of the axon depolarizes the adjacent segment.

Distinguish the resting membrane potential and the action potential.

The resting membrane potential is normally negative and, when threshold is reached, is greatly depolarized. The action potential is the brief but large change in neuronal polarization.

Describe the resting membrane potential

The resting membrane potential is the potential difference across the membrane of a neuron of about -50 to -80 millivolts. It is normally negative so that it can respond to a stimulus quickly.

What are narcotic analgesics, and where do they act?

They act at opioid receptors.

What are stimulants and hallucinogens, and where do they act?

They act by increasing excitatory synaptic potentials.

At what receptors do barbiturates, alcohol, and benzodiazepines act?

They all act on GABA-A receptors

What are the endocannabinoids, and how do they function?

They are an endogenous ligand of cannabinoid receptors, and analog of marijuana produced by the brain. They act as retrograde messengers conveying messages form the postsynaptic cell to the presynaptic cell.

What are the forces that create membrane potentials?

They are diffusion, which forces cells to move from high concentration to low, and electrostatic forces, which is when like repels like and opposite attracts opposite.

Why do withdrawal symptoms occur?

They occur because of drug-induced tolerance. There are alterations to receptor number or affinity or alterations in receptor-coupling to effectors (ion channels or second messengers)

Describe the refractory period.

This describes when the axonal membrane is unresponsive to any other stimulus. The absolute refractory phase is a brief period following the production of an action potential, where no stimulus can induce another action potential. The relative refractory period is when only a strong stimulation can produce another action potential.

What is meant by the therapeutic index (LD50/ED50) or margin of safety?

This is comparison of doses that exert beneficial effects versus doses that exert toxic effects

Define tricyclic, SSRI and MAO-I

Tricyclic antidepressants are a class of drugs that act by increasing synaptic accumulation of serotonin and norEPI. SSRIs block the reuptake of serotonin. MAO-I is a monoamine oxidase inhibitor, an enzyme that breaks down and inactivates monoamine transmitters

What disease processes involve abnormalities in acetylcholine neurotransmission?

What disease processes involve abnormalities in acetylcholine neurotransmission?

How do voltage-gated ion channels contribute to an action potential?

When the membrane potential reaches a certain point, they change shape. For example, the voltage-gated Na+ channel is ordinarily closed, but when it becomes depolarized to threshold levels, it opens and allows Na ions through.