BBH 203 EXAM 2

Outcome of agonist/antagonist

-If a neurochemical normally has an inhibitory effect, the action of an agonist would increase this inhibitory effect -Antagonist would result in less inhibition -Strengthens the signal itself but not deciding if inhibitory or excitatory

Reuptake effects

-Inhibit reuptake of dopamine--> cocaine, amphetamine, and methylphenidate (Ritalin) -Dopamine agonists (enhance dopamine) -Inhibit reuptake of serotonin--> fluoxetine (Prozac) (antidepressant medication) -slow reuptake --> remain in synapse

Opioids

-Interact with endorphin receptors -most effects produced from acting presynaptically to inhibit release of neurotransmitters -Pain relief, relaxation, sense of euphoria -Opiates - legit medical purposes -Derived from sap of opium poppy -Morphine, codeine -Heroin -Pain management, cough suppression and treatment of diarrhea -Oxycontin = most frequently used -ADDICTIVE -3 receptors bind them

Insula

-Involving insula = increased desire for drug -Activity in insula correlates with participants ratings of their craving for their drug of choice, and strokes that damage to the insula eliminates the urge for the addictive drug

Individual Differences in Response to Drugs

-Larger bodies have more blood, need more of drug for same effect -Gender: diluted by water in muscles -Genetics

Three receptors that bind opioids

-METABOTROPIC -mu, delta, kappa -fourth was found later: like-1 (ORL 1) *highest affinity for mu receptor

Acetylcholinesterase (AChE)

-Manufactured from cholinergic neurons -Enzymes that break down Ach -Recycles choline (recaptured in synapse) to build more acetylcholine

Administration of Drugs

-Method of administration leads to different effects on nervous system -Inhaling, eating, and injecting -Injecting is the fastest mechanism -> pumps right from blood to brain -Slowest = eating/ ingesting

Adenosine triphosphate ATP and its byproducts

-small molecule -byproduct usually adenosine -Neuromodulators in CNS and in connections between autonomic neurons and the vas deferens, bladder, heart, and gut -Pain modulation -Adenosine results from the breakdown of ATP -high adenosine levels are inhibitory

Monoamines

-small molecules -6 -subgroups -All subject to reuptake from synaptic gap following release -Within axon terminal, monoamines not encased in a vesicles are broken down by the action of the enzyme monoamine oxidase (MAO) -outside neurons, catecholamines, are broken down the enzyme catechol-O-methyl-transferase (COMT)

Amino Acids

-small molecules -glutamate, GABA, glycine and others

NMDA and AMPA usually are found near each other on the same post synaptic receptor

-sodium moving through nearby AMPA will depolarize post synaptic cell -once depolarized, magnesium ions from NMDA are ejected allowing it to open in response to binding of glutamate

Methamphetamine

-serves as a dopamine agonist in an interesting manner (enhances activity of) -pump dopamine in absence of action potential into synapse -and block reuptake -dopamine trapped in gap

Small Molecules

*vital role in neuron signaling* Includes amino acids, ACh and monoamines -Typically synthesized in the axon terminal buttons -So simple don't have to take the same course of a normal neurochemicals; manufactured in button -Vesicles are reused -Small amounts of calcium needed for exocytosis -Large amounts needed to activate postsynaptic receptors

Withdrawal

- occurs when substance use is discontinued or reduced -Opposite of the effects caused by the drug -Sedative = agitated -Stimulant = lethargic (sluggish) -Avoiding withdrawal is not the sole source of compulsive drug seeking and use

Neurochemical Storage

-Drugs can have an antagonist effect to interfere with storage in vesicles **Reserpine- used to reduce blood pressure and psychosis -Blocks the uptake of monoamines into vesicles -Result: small amounts of monoamines available for release -Interference w serotonin causes depression

Glutamate Receptors

-8 metabotropic identified -named mGluRs -3 ionotropic named after what activates them -NMDA, AMPA, kainate receptor

Cannabis

-Active ingredient THC is an endogenous cannabinoid receptor agonist -2 types of cannabinoid receptors CB1 and CB2 -Hippocampus and prefrontal cortex -Negative effects on memory formation, attention, and working memory -Inhibit glutamate release -Mild euphoria, perceptual distortion, hallucination, and depression -Schizophrenia -Higher likelihood **does not lead to it**

Enzyme Degradation

-At cholinergic synapse, acetylcholinesterase (AChE) deactivates Ach -Drugs that interfere with AChE boost Ach activity -Helpful in conditions like muscular disorder myasthenia gravis -Normal ach activity, too much Ach can produce autonomic disruptions, involuntary movements, and paralysis and death

Norepinephrine

-Catecholamine (monoamine) (small molecule) -increases arousal and vigilance; primary neurotransmitter in the sympathetic nervous system -Medulla, pons, hypothalamus, brainstem

Dopamine

-Catecholamine (monoamine) (small molecule) -neurotransmitter involved with movement, motivated behaviors and the processing of rewards -movement issues -addiction issues -cells releasing dopamine start in midbrain -form neuromodulating system -dopamengeric pathways

Epinephrine

-Cathecolamine (monoamine) (small molecule) -Neurohormone (hits the bloodstream activating things throughout the body); regulation of eating, blood pressure -Medulla -Adrenalin rush = Release of epi from adrenal glands above the kidneys into the blood supply

Neurotransmitters

-Direct synapses -Wiring transmission -Chemical messenger that communicates across a synapse -Ionotropic= rapid communication -Metabotropic= last as long as several hours -Travel one way: presynaptic to postsynaptic

Gasotransmitter

-Dissolve easily in lipids -Can diffuse through membranes without vesicles or a release mechanism -Act on receptors located within the cell rather than embedded in the membrane -Break down quickly without use of enzymes -Transfer info from postsynaptic neuron to presynaptic neuron, not the other way around (retrograde signaling) -transfer info from one cell to another -NO and CO

Receptor Effects

-Most prevalent -Drug behaving like a chemical that a receptor is looking for -Or block synaptic activity by occupying a binding site on a receptor without activating the receptor

Cholinergic Neuron

-Neurons that use Ach as their major neurochemical -Obtain building block choline from breakdown of dietary fats and breakdown of existing Ach -Obtain building block acetyl coenzyme A (acetyl Co A) from metabolic activities of the mitochondria -Enzyme choline acetyltransferase (ChAT) acts on building blocks to produce Ach -ChAT is only found in neurons producing Ach (cholinergic)

Neuromodulators

-Non-directed; CSF -Volume transmission -Effect more global processes (attention and assessment of threat, saliency, novelty and reward) -Communicates with target cells more distant than the synapse by diffusing away from the point of release -Released from axon varicosities (unmyelinated); but can be co released from an axon terminal with a neurotransmitter -Can remain in CSF for extended periods of time where they can continue to affect CNS -Restricted to metabotropic receptors -Can interact with pre and post synaptic cell

Acetylcholine

-Otto Loewi - first chemical messenger discovered -Small molecule (primary neurotransmitter of ANS --> parasym (always Ach- rest and digest) sym --> norepi and ACh (fight or flight)) -Consists of acetate and choline -Cholinergic Neuron -Dorsolateral pons- sleep -Basal forebrain- perceptual learning -Medial septum- hippocampus (memory), hypothalamus (drives, thirst, hunger), and amygdala (fear, aggression, memory w emotion) -Deteriorate in Alzheimer's disease -2 major subtypes: nicotinic and muscarinic receptors

Glycine and NMDA

-Plays excitatory role with glutamate at NMDA -Produce lower body temperatures typical of sleep -Glycine administration as a treatment for insomnia not approved yet *Glycine is usually inhibitory

Neurohormone

-Released into bloodstream; non-directed -Secreted by special neurons in the blood -Interact only with cells with specialized receptor sites to receive them -Many cells that produce --> hypothalamus, adrenal glands and enteric nervous system

Gasotransmitters

-Typically synthesized in dendrites -No exocytosis -Diffuses out once it is produced -Exceptionally small -Does not bind to postsynaptic receptors -Diffuses into other cells -Activates production of a secondary messenger in system

Neuropeptides

-Typically synthesized in soma and have to be sent to terminal buttons -Vesicles only used once -Large amount of calcium for exocytosis -Small amounts needed to activate post synaptic receptors -Primarily activate metabotropic receptors (G proteins) -Receptor itself not bound to a channel -More control over activating/ deactivating effects

Treatment of Addiction

-Withdrawal produces changes in accumbens, involving glutamate signaling -Use meds to target glutamate activity in accumbens to inhibit drug seeking -Mixed results -Methadone for heroin; prevents withdrawal symptoms -Alcoholics treated with disulfiram or Antabuse which interferes with ALDH enzyme in metabolizing alcohol; unpleasant symptoms -Vaccinations to target nicotine, meth, cocaine, and heroin developed -Stimulate immune system to bind problem drug and prevent or delay movement across blood brain barrier into brain (May use higher quantities to overcome the vaccination) -Environment plays a role in drug use

Wiring Transmission

-chemicals diffuse from one cell to impact an adjacent cell or cells through private, highly localized channels -neurotransmitters

Caffeine

-adenosine antagonist (lowers adenosine) -Reduces inhibitory effect of adenosine -Adenosine inhibits glutamate -Glutamate is usually excitatory -Caffeine fits the key spot for adenosine; glutamate increases in the body -Increases blood pressure and heart rate, improves concentration and wards off sleepiness -Increases release of dopamine in nucleus accumbens dependence -Withdrawal: headaches and fatigue -Correlated with lower rates of parkinsons disease, particularly in men -Most commonly used stimulant in the US

Psychoactive Drugs

-administered to obtain a particular psychological benefit -Circumvent (find a way around) the protective systems of blood brain barrier to gain access to CNS

Glutamate

-amino acid (small molecule) -"glutamic acid" -long term memory -most common excitatory neurochemical in CNS -a chemical that nerve cells use to send signals to other cells -used by 90% of synapses in brain -mitochondria -taken up quickly by astrocytes and neurons -extended action --> toxic -ionotropic or metabotropic receptors

Gamma-aminobutyric acid (GABA)

-amino acid (small molecule) -Major inhibitory neurochemical of CNS (involved in 40% of synapses in CNS) -INHIBITION -Mood -Seizure threshold -Synthesized from glutamate -3 types of receptors

Glycine

-amino acid (small molecule) -Used to build other proteins -SLEEP -Acts directly as am inhibitory neuron by opening ionotropic chloride receptors -primarily in synapses formed by spinal cord interneurons and smaller numbers elsewhere -removed from synapse by reuptake -plays excitatory role with glutamate at NMDA

Barbiturate

-anesthesia and control of seizures -sedation effect -GABA agonist (enhance GABA) -can activate GABAa receptor without GABA present

Curare

-block nicotinic receptors -Derived from plants -Used to relax muscles -Snake venom acts in the same way- occupy same nicotinic receptor without breaking down or being released (ACh cant stimulate) -cant breathe!!

Deactivation of Neuropeptides

-can include diffusion away from synapse or enzymatic degradation -Unlike small molecules, not deactivated by reuptake

Deactivation of Small Molecules

-can include reuptake or enzyme degradation ****Reuptake only happens with small molecules

Ionotropic Receptor

-direct or fast case; a receptor protein whose recognition cite is located on the same structure

Cocaine

-dopamine reuptake inhibitor; dopamine remains in the cleft and activates receptors for a longer period, heightening the effects -Lower doses: alertness, elevated mood, confidence and a sense of well being -High doses: symptoms similar to schizophrenia -Tactile hallucinations (bugs on skin) -Freud: recommended antidepressant -Appetite suppressant -Coke used cocaine and subbed caffeine when found negative effects

Catecholamines

-dopamine, norepi and epi -Outside neurons, broken down by the enzyme catechol-O-methyl-transferase (COMT) -All neurons containing and catecholamine also contain the enzyme tyrosine hydroxylase (TH) -Synthesized from the amino acid tyrosine -monoamine (small molecules)

Endorphins purpose

-endogenous morphine -Natural opioids help us escape emergency situations in spite of pain

Agonist/ antagonist is NOT the same as

-excitation and inhibition

Neurochemical Release

-exocytosis -drugs modify release of neurochemicals in response to an action potential -Some interact with presynaptic auto receptors -Others directly interact with proteins responsible for exocytosis (release of neurochemical into synapse) -Exocytosis is promoted by agonists and blocked by antagonists

Nitric Oxide (NO)

-gasotransmitter -CNS and PNS -gas that produces signaling between neurons -smooth muscle -relax smooth muscle cells in blood vessels -erection and possible retrograde signaling -Short living free radical produced by actions of enzyme nitric oxide synthase (NOS), which is found in a small number of neurons, on the amino acid arginine

Most common excitatory neurochemical?

-glutamate

Melatonin

-indolamine (monoamine) (small molecule) -Neurohormone; derived from serotonin -pituitary gland -sleep -Secreted in the dark and breaks down rapidly in response to light; especially light in short wave or blue end of the spectrum

Serotonin

-indolamine (monoamine) (small molecule) -synthesized from tryptophan -Enteric nervous system o 95% of serotonergic neurons -Raphe nuclei of the pons, medulla and cerebellum o5% (Regulates mood, sleep, appetite, aggression, and dominance (SSRIs)) -more rostral --> wiring -medulla --> volume -Influence motivation to consume carbohydrates (over eating)- body releases serotonin (improves mood) -depression --> lower than average serotonin

N-methyl-D-aspartate receptor (NMDA)

-ionotropic glutamate receptor -long term memory -Voltage and ligand dependent -Will not open unless glutamate is present AND postsynaptic membrane is depolarized at the same time -at rest --> receptors blocked by magnesium -Allows positively charged sodium and calcium into the cell, which further depolarizes

Alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor (AMPA)

-ionotropic glutamate receptor -most common -operate by controlling a sodium channel -lays close to NMDA

Kainate Receptor

-ionotropic glutamate receptor -operate by controlling a sodium channel

GABAa

-ionotropic post synaptic chloride channels which allow negatively charged cl ions to enter the cell

Nicotinic receptors

-ionotropic receptors (direct/fast) -evolved to react with ACh -responds to nicotine -found at neuromuscular junction

Tolerance

-lessened effects as a result of repeated administration -Higher dosage needed for same effects Changes in: -Enzymes- produce more to break down "foreign chemical" -Receptor density- increase; more of chemical for same effect -Learning: rats & overdose

GABAa and drugs

-many binding sites -one activated by GABA itself -others by benzodiazepines, alcohol and barbiturates

Muscarinic Receptor

-metabotropic (G protein) -reacts with ACh -responds to muscarine (mushroom) -found in heart and other smooth muscle -more common

GABAb

-metabotropic potassium channels which allow positively charged K to leave the cell

Indolamines

-monoamine (small molecule) -serotonin -melatonin

Histamine

-monoamine, small molecule -synthesized from histidine -Associated with wakefulness •Insomnia •Anti-histamine used to treat insomnia -Use antihistamines to treat allergies -Most released by immune system cells and blood cells -Neuromodulator in the brain

Metabotropic Receptors

-more far reaching; activate farther areas; more options -Activating entire body; advantageous

Volume Transmission

-neurochemicals diffuse through the extracellular fluid and CSF to influence cells located some distance away from the releasing cell -neuromodulators

Neuropeptides

-neuromodulators and neurohormones -Manufactured in neural cell body and must be transported to the axon terminal- (Could take more than one day) -Possible to run out of neuropeptides during periods of active signaling -Often coexist in the same neuron with a small molecule messenger and are co released to modify its effect -A single neuron can contain and release several different neuropeptides -All metabotropic receptors -Deactivation occurs in synapse through diffusion or enzymatic degradation

Insulin and Cholecystokinin (CCK)

-neuropeptide -Digestion -Neuromodulation and Neurohormone functions -Processing of nutrients

Oxytocin and vasopressin

-neuropeptide -Released from pituitary gland -Neuromodulators and hormones

Endorphins

-neuropeptide -Substances that act on the same receptors as opioids such as heroin -Pain reduction -Feelings of well being

Substance P

-neuropeptide -perception of pain

Nicotine

-nicotinic cholinergic receptor agonist -Stimulates cholinergic receptors to release dopamine in accumbens -In CNS: glutamate and dopamine agonist; hence stimulant -2nd most common used stimulant in the US -Increase HR and BP, promotes release of adrenaline, reduces fatigue, and heightens cognitive performance -PNS: muscular relaxation -May contribute to mental illness, specifically depression -Withdrawal: inability to focus and restlessness

Withdrawal

-occurs when substance use is discontinued or reduced -Opposite of the effects caused by the drug -Sedative = agitated -Stimulant = lethargic (sluggish) -avoiding withdrawl is not the sole source of compulsive drug seeking and use

Metabotropic Receptor

-protein structure in postsynaptic neuron containing a recognition cite and a G protein needed to open channel; indirect or slow -longer effects -greater variety of responses

Amphetamine

-stimulates release (without an action potential) and inhibits reuptake of dopamine/ norepinephrine -More released -And reuptake blocked -Lower doses: alertness, elevated mood, confidence and a sense of well being -High doses: symptoms similar to schizophrenia -Tactile hallucinations (bugs on skin) -Show repetitive behaviors: chewing movements or grinding of teeth -Developed as a treatment for asthma -Ward off fatigue -Suppress appetite -Cheap and easy to manufacture

Ecstasy (MDMA)

-stimulates release of serotonin, oxytocin, norepinephrine and dopamine -Oxytocin bonding experience; social situations; mother child bond (breastmilk) -Why people touch everything and are more social -Serotonin = affects mood; elevation in mood -Dopamine = elevation in euphoria -Damages serotonergic neurons - strongest effect -Pumps monoamines into the gap and trapped

Neurochemicals

-substances released from one cell that produces a reaction in a target cell 3 General Categories: -Neurotransmitter, neurohormone, neuromodulator Fall into 3 Classes: -small molecule, neuropeptides, gasotransmitters

Catecholamine Synthesis

-tyrosine -L-dihydroxyphenylalanine (L-dopa) -Dopamine (DA) -Norepinephrine -Epinephrine

Cholinergic Neurons

-use ACh as major neurochemical -manufacture AChE -neuromodulation system in the brain -deteriorate in Alzheimers -2 subtypes: nicotinic and muscarinic (nervous system) --> get names from what activates them

Beyond basic defintion of neurochemicals, neuroscientists agree on 3 criteria

1. substance must be present within a presynaptic cell 2. substance is released in response to presynaptic depolarization 3. the substance interacts with specific receptors on a postsynaptic cell

If adenosine levels rise in extracellular fluid, 3 types of metabotropic receptors are activated...

A1- inhibits release of glutamate, Ach, Norepi, serotonin and dopamine A2- facilitates the release of glutamate and Ach while inhibiting the release of GABA *dont need to know third

Mesocortical System

Dopaminergic Pathway -Planning and executive functioning -Schizophrenia, attention deficit hyperactivity disorder -Tegmentum to prefrontal cortex

Mesolimbic System

Dopaminergic Pathway -Rewards

Nigrostriatal Pathway

Dopaminergic Pathway -80% of brains dopamine -Voluntary movement -Damage: Parkinson's Disease -Difficulty initiating movements

Receptor Subtypes for Dopamine

D1 --> D5 -All are slow metabotropic variety -D1 and D5 = excitation •Hippocampus and hypothalamus -D2, D3, D4 = inhibition •Frontal lobe, thalamus, and brain stem -Both found in basal ganglia, nucleus accumbens and olfactory cortex

Most common inhibitory neurochemical?

GABA

Alcohol

GABAa receptor agonist (more GABA) *normally produces neural inhibition* -NMDA glutamate receptor antagonist (lowers glutamate) -Stimulates dopaminergic reward pathways -Rapid tolerance -Increase production of liver enzymes to eliminate from the system -Damaging effects on health -Influences memory -Depressant- physiologically depresses body- not mood -Drinking in moderation actually decreases risk of death -Heritability may explain 50% of differences in susceptibility to alcohol dependence -Membranes, ion channels, receptors and enzymes are all effected

Types of Neurochemicals

SIZE -small molecules = 1-2 amino acids -neuropeptides= 3-36 amino acids (can act as a neurotransmitter, neurohormone, or neuromodulator -gasotransmitters = rare and unique

LSD

Serotonergic agonist -Hallucinogen -Tolerance, but not addiction or withdrawal (no interaction with dopamine) -Flashbacks - intrusive or unwanted visual hallucinations- even year's after **Chemically similar to serotonin

Most neurons release

a small molecule along with a neuropeptide or a gasotransmitter

Neurons that use ACh as their major neurochemical

cholinergic neurons -also manufacture enzyme acetylcholinesterase (AChE)

Agonist

drugs that enhance the activity/ effect of a neurotransmitter

Antagonist

drugs that reduce activity/ effect of a neurotransmitter

Botulism

fatal condition produced by bacteria in spoiled food, in which a toxin produced by bacteria prevents the release of ACh *ACh = neuromuscular junction = muscle issues

stimulants

increase alertness and mobility

Benzo and alcohol

increase the receptors response to GABA but only when they occupy binding sites at the same time GABA is present

ACh is the

primary NEUROTRANSMITTER at the neuromuscular junction, synapse between neuron and muscle fiber

benzodiazepines

tranquilizers

Drugs not influencing dopamine or nucleus accumbens are often

used habitually but do not cause the craving and compulsive use associated with addiction LSD! -damage to these areas reduces drug dependancy