Medications and Behavior Exam 1, Becknell (Chapters 1-4)

Sensory Neuron (afferent): PNS to CNS

Motor Neuron (efferent): CNS to PNS

Interneuron: bridge communication between the two in the CNS

Classes of Neurons

Axon Hillock

point on the soma where the axon and electrical signal both originate

Neurotransmitter Reuptake

a process where a neurotransmitter is reabsorbed by the axon that released it

Ion Channels

'gates' that can be open or closed, allowing ions to pass through

Resting Potential

electrical charge across the cell membrane of a resting neuron

Graded Potential

a shift in the electrical charge in a tiny area of a neuron

Action Potential

complete depolarization of the neuronal membrane from -70 mV to approximately +40mV

The neuron depolarizes as sodium ions flow into the cell and the area then contains a positive charge. Sodium ions go into the cell and potassium ions slowly go out of the cell due to the electrical and concentration gradients

What happens during an action potential?

Node of Ranvier

small gap between myelinated segments where axonal membrane is exposed; increase speed of impulses

Ionotropic Receptor

when a receptor directly controls an ion channel

Metabotropic Receptor

when a receptor is not part of the ion channel and other proteins are involves in controlling the ion channel; utilizes second messengers

Phosphoralation

process of adding a phosphate group to a molecule

Excitatory Postsynaptic Potential (EPSP)

a slight depolarization of a postsynaptic cell, bringing the membrane potential of that cell closer to the threshold for an action potential

Inhibitory Postsynaptic Potential (IPSP)

an inhibitory hyperpolarization of the postsynaptic membrane of a synapse caused by the liberation of a neurotransmitter by the terminal button

Neural Integration

the process by which inhibitory and excitatory postsynaptic potentials summate and control the rate of firing of a neuron

Presynaptic Facilitation

action of an axoaxonic synapse at a synaptic terminal that increases the neurotransmitter released by presynaptic membrane

Presynaptic Inhibition

action of an axoaxonic synapse at a synaptic terminal that decreases the neurotransmitter released by presynaptic membrane

Autoreceptors

receptors that respond to the released transmitter by inhibiting further synthesis and release

Heteroreceptors

receptors located on the presynaptic button that are sensitive to a neurotransmitter from another neuron

Neuromodulators

a substance produced and released by neurons or glia that alters cell functioning; they may alter the effects of neurotransmitters at synapses and may act at greater distances from the releasing cell, unlike neurotransmitters

Acetylcholine

What was the first neurotransmitter to be discovered?

- Acetylcholine (excitatory)

- Norepinephrine (both)

- Dopamine (inhibitory)

- Serotonin (inhibitory)

- GABA (inhibitory)

- Endorphins (inhibitory)

- Glutamate (excitatory)

- Glycine (inhibitory)

- Substance P (excitatory)

- Anandamide (inhibitory)

- Adenosine (inhibitory)

List of Major Neurotransmitters/Neuromodulators

- be synthesized and stored in the presynaptic neuron

- be released into the synapse when the neuron fires

- cause a postsynaptic effect after it interacts with a receptor

- there must be some mechanism for degradation or reuptake

What are the qualifications of a neurotransmitter?

Long-Term Potentiation

the postsynaptic membrane can now more readily depolarize when stimulated

Excitotoxicity

excessive exposure of postsynaptic neurons to glutamate

Nocioceptors

pain receptors to the dorsal horn of the spinal cord

Neocortex

"new cortex"; outermost surface of the brain/cortex and most recently evolved

Limbic System

portion of the brain most closely associated with emotional expression and motivation

Reticular Activating System

the part of the brain that is involved in attention, sleep, and arousal

Mesolimbic-Cortical System

the system of dopamine-containing neurons that originate in the ventral pons, project through the nucleus accumbens and septum, and terminate in the frontal cortex, which mediates the reinforcing effects of eating, sex, and addictive drugs

Orexin

neurotransmitter secreted by the hypothalamus; triggers hunger

Pituitary Gland

produces and secretes a variety of essential hormones

Tardive Dyskinesia

severe motor disorder characterized by facial tics, lip smacking, tongue extensions, and rapid eye blinking; can be cause by long-term use of antipsychotic medication

Pharmacokinetics

the science of how drugs are absorbed, distributed to body tissues, and eliminated from the body after metabolism

Chemical Name

the name that describes the chemical composition and molecular structure of a drug

Brand Name

the patented trade name for a drug (Prozac)

Generic/Trade Name

a medication that can be made by many different companies; costs less than brand-name medicines but have to be pharmacologically equivalent (fluoxetine)

Drug Absorption

mechanisms by which drugs get into the blood stream and distributed throughout the body

- Orally (patient administration, delayed absorption)

- Inhalation (absorbed through lungs into blood stream; rapid)

- Intravenous (rapid and precise, directly in blood stream)

- Intramuscular (prolonged absorption; difficult patient administration)

- Transdermal (on skin; absorption is slow but prolonged)

- Subcutaneous (injection/implantation that can last long times)

- Intraperitoneal (directly into abdominal cavity; not used on humans)

What are the different ways to administer a drug?

Blood Brain Barrier

mechanism that prevents certain molecule from entering the brain but allows others to cross

Depot Binding

the binding of a drug to inactive sites; drug comes back into bloodstream due to concentration gradient when some of the other supply is excreted

Tissue Equilibrium

when the concentrations of a drug in the blood and tissues are essentially the same

Cytochrome P450

integral enzymes involved in the metabolism of drugs; produced by cells in the liver

Dose Response Curve

a graph of the magnitude of an effect of a drug as a function of the amount of drug administered

Respiratory Depression

decrease in respiratory rate

Tolerance

a progressive decrease in a person's responsiveness to a drug

Cross-Tolerance

tolerance for a substance one has not taken before as a result of using another substance similar to it

Downregulation

decrease in neurotransmitter synthesis or release caused by drug action on target receptors; may also involve decreases in receptor availability

State Dependent Learning

learning that becomes associated with the conditions under which it occurred, so that it is best remembered under the same conditions

Therapeutic Index

the ratio between the toxic and therapeutic concentrations of a drug

Placebo

a fake drug used in the testing of medication

Double-Blind Procedure

an experimental procedure in which both the research participants and the research staff are ignorant (blind) about whether the research participants have received the treatment or a placebo

Pharmacodynamics

what the drug does to the body

Agonist

a drug that facilitates neurotransmission

Antagonist

a drug that inhibits neurotransmission

Reuptake

a neurotransmitter's reabsorption by the sending neuron

Selective Serotonin Reuptake Inhibitors (SSRIs)

block the serotonin reuptake transporters so that there is more serotonin available in synapses

- Dopamine

- Epinephrine

- Norepinephrine

*** Catecholamines (DEN)

- 5-Hydroxytriptamine (5-HT)

- Monoamine, but not a catecholamine

- Receptors: mostly metabotropic

- Synthesized from: tryptophan

*** Serotonin

- Nigra Striatal: substantia nigra -> caudate nucleus / putamen; implicated in Parkinson's

- Mesolimbic: reward, nucleus accumbens

- Mesocortical

- Tuberoinfundibular: prolactin (breast hormone)

*** Dopamine Pathways

- First discovered neurotransmitter (Loewi)

- Receptors: muscarinic (metabotropic), nicotinic (ionotropic)

- Synthesized from: choline

Acetylcholine (***receptors)

- Synthesized from: tyrosine

- Receptors: metabotropic

- Monoamine Oxidase breaks it down

Norepinephrine

- #1 excitatory neurotransmitter

- Involved in long-term potentiation

- Receptors: ionotropic and metabotropic

Glutamate

- #1 inhibitory neurotransmitter

- Receptors: ionotropic and metabotropic

- Synthesized from: glutamate

GABA

- Peptide

- Associated with pain ("P"ain)

Substance P

- Rostral (toward beak), Caudal (toward tail)

- Anterior (front), Posterior (back)

- Superior (higher), Inferior (lower)

- Dorsal (toward back), Ventral (toward stomach)

- Lateral (away from middle), Medial (toward middle)

- Proximal (toward body), Distal (toward end of limb)

Anatomical Directions

- Serotonin

- Dopamine

- Epinephrine

- Norepinephrine

What neurotransmitters are monoamines?

Henderson-Hasselbalch Equation

measure of fat solubility

- Philic = love, phobic = repulsion

- Liver makes items lipophilic (fat soluble), and detoxifies xenobiotics

- Kidneys make items hydrophobic for excretion

- Drug metabolized in liver and excreted through kidneys

*** Metabolism/excretion and suffixes

Blood-Brain Barrier

makes it more difficult for substances to pass through, but fat soluble ones get to brain by diffusion

Drug/Elimination Half-Life

the time it takes for the amount of drug in the body to be reduced by half

- How much of a drug do we give?

- Can't give maximum amount for maximum effect, all drugs have a therapeutic window

Dose-response relationship

Threshold Dose

minimally effective dose, just large enough to produce detectable change

Maximum Dose

greatest degree of response achievable with drug

- High: take more for effects (benzodiazepines)

- Low: take less for effects (lithium carbonate, barbiturates); high risk of toxicity

*** High vs Low Therapeutic Index

Opiates

What class of drugs has the fastest tolerance?

ETOH --alcohol dehydrogenase-> acetaldehyde --alcohol dehydrogenase-> acetic acid -> CO2 and H2O

*** Process of alcohol breakdown

Increased ETOH consumed -> increased liver enzymes -> increased ETOH tolerance

- Metabolic tolerance

*** Process of alcohol tolerance

***ETOH

ethyl alcohol, drinkable alcohol

"poop out"

Fun term: Prozac =

Cellular Tolerance

cells adapt to repeated exposure to drugs

Metabolic Tolerance

repeated exposure to the drug causes the metabolic machinery of the body to become more efficient at clearing the drug

Associative Tolerance

tolerance can be displayed in one context but not another; if in a new environment, higher chance of overdose

Behavioral Tolerance

animals intoxicated with ETOH before learning a motor task will perform better on that task when "under the influence"; called state-dependent learning

- Associative: classical

- Behavioral: operant

What types of conditioning are associative and behavioral tolerance?

Noecebo

inert substance with negative supposed effects

- Sleep

- Interests

- Guilt

- Energy

- Concentration

- Appetite

- Psychomotor

- Sex/suicide

***SIGECAPS

SSRI's (PaPaLZaC-FaPESaC)

> Prozac - fluoxetine

> Paxil - paroxetine

> Lexapro - escitalopram

> Zoloft - sertraline

> Celexa - citalopram

SNRI's (EPCaR-VaDaDaM)

> Effexor - venlafaxine

> Pristiq - desvenlafaxine

> Cymbalta - duloxetine

> Remeron - mirtazapine

Atypicals (WaDE-BaTaK)

> Wellbutrin/Zyban - bupropion

> Desyrel - trazodone

> Esketamine - ketamine

Tricyclic Antidepressants (TEPA-IANaC)

> Tofranil - imipramine

> Elavil - amitriptyline

> Pamelor - nortriptyline

> Anafranil - clomipramine

Mood Stabilizers and Anticonvulsants

> Lithium

> Neurontin

> Depalcote

> Lyrien

< Topomax

< Abilify

< Tegretol

MAOI's

> Nardil

> Marplan

***Antidepressants/Mood Stabilizers (be able to match/recognize these)

- Prevalence: twice as high in women; annual 10%; lifetime 17%

- Commonly begins in late adolescence or early adulthood

Depression basic info:

- Give medication

- Increase activity level

- Therapy/counseling

- Transcranial magnetic stimulation

- Electroconvulsive therapy

- Deep-brain stimulation

Depression treatment:

- Low thyroid

- Low vitamin D

Rule-outs for depression:

- Low monoamine = low neurotransmitters

- Initial evidence: effective drugs increased these levels

- Low monoamines due to downregulation as a result of increased autoreceptor activity

*** Monoamine Hypothesis:

- Lag time between drugs and effects was an issue

- Neuronal changes: result of BDNF, key protein which is growth factor for neuron survival, receptor growth, and neurogenesis

- Mechanism: BDNF and downregulation of monoamine autoreceptors

- Stress increases cortisol which leads to BDNF downregulation

*** Revised Monoamine Hypothesis:

BDNF

brain derived neurotrophic factor; essential for neuron synthesis, growth, and survival

- BDNF = "Miracle Gro for the brain"

- contributed to understanding of BDNF

Ronald Dumon's contribution:

- Accidental discovery, originally for schizophrenia

- a dirty drug

- Increase BDNF synthesis

Tricyclic Antidepressants:

Dirty Drug

drugs with bad side effects

- ***Block acetylcholine receptors, causing anticholinergic effects

- Block histamine receptors

- High overdose potential

Tricyclic side effects:

Anticholinergic Effects

dry mouth, dizziness, hypotension, constipation, etc. (less lubricant all over body typically)

- Accidental discovery, originally for tuberculosis

- Inhibit enzymes that degredate monoamines

Monoamine Oxidase Inhibitors: