psy 209 exam 2 🧠

which chemicals are a part of the catecholamine system?

• dopamine

• norepinephrin

• epinephrin

which chemical is a part of the cholinergic system?

acetylcholine

what’s the criteria of a neurostransmitter?

• exist in presynaptic terminals (output area in vesicles)

• created/synthesized in presynaptic cells

• released when action potential reaches axon terminal

• has corresponding receptors on the postsynaptic membrane

• produces changes in postsynaptic potential

• if release is blocked, changes in postsynaptic cell is prevented - can influence neurotransmitter to change receptors

dopamine (DA)

• part of the catecholamine system

• has 2 pathways: mesolimbocortical & mesostriatal

• produced in midbrain and action potential causes its release into the synapse, binds to dopamine receptors

• makes us crave, desire, want to acquire, etc. something (motivation to pursue goals)

  • causes us to place value on motivational events & search them out or crave them

• receptors are metabotropic

DA mesolimbocortical pathway

found in the VTA

• ventral tegmental area → nucleus accumbens → cortex & hippocampus

• also described as: midbrain → limbic system → cortex

role: motivation, reward, processing, decision-making

• critical in driving the pursuit of both natural & drug rewards

DA mesostriatal pathway

found in VTA

substantia nigra → striatum (caudate & putamen)

• also descried as: midbrain → basal ganglia

role: goal-directed motor actions

• contributes to Parkinson’s disease

what diseases are influenced by dopamine?

Parkinson’s disease

• dysfunction in nigrostriatal pathway (substantia nigra → dorsal striatum)

norepinephrine

• part of catecholamine system

• widely expressed in the CNS (projects to many brain areas)

• has effect over metabatropic receptors

• synthesized in brain stem

  • enzymes synthesize dopamine signals to create norepinephrin

• when released into brain, it binds to its metabotropic G-protein coupled receptors

locus coerulleus

part of norepinehrine pathway that sends signals to brain to be aroused

norepinephrin receptors (3)

α₁, α₂, β

role of norepinephrine

preparing brain & body to respond to stressful/dangerous situations

• the neurotransmitter that drives fight or flight response & PTSD

• influences sympathetic nervous system (PNS)

what diseases are influenced by norepinephrine?

PTSD (drives the fight-or-flight response because of its effects over metabotropic receptors)

epinephrine

• part of catecholamine system

• can be converted into norepinephrine

• adrenaline: cannot cross the blood-brain barrier, but causes PNS to increase arousal

• increases cardiac output and raises glucose levels (responsible for energy)

• primarily projects to the brain stem, spinal cord, and hypothalamus

what diseases are influenced by epinephrine?

really none that we’ve discussed

acetylcholine (Ach)

• endogenous ligand of the cholinergic system

• alters cognition & perception; plays role in nicotine addiction

• responsible for Alzheimer’s, mediates nicotine addiction, modulates autonomic nervous system

• 1st discovered neurotransmitter

• affects the PNS

• binds to ionotropic & metabotropic receptors

how was acetylcholine discovered?

Otto Loewi showed that a neurotransmitter could be produced and affect the nervous system

• stimulated the vagus nerve in one heart, then heart released acetylcholine, slowing down heart rate

• when heart 2 was placed in this solution, heart rate slowed down

ionotropic receptors

ligand-gated ion channels; fast acting

• when Ach binds, there’s typically an excitatory neurotransmission when Na+ enters post-synaptic cell (depolarizes cell)

• labeled as nicotinic Ach receptor, as they respond to nicotine and Ach

metabotropic receptors

G-protein coupled; slow-acting

• when Ach binds, activates G-protein that results in either inhibitory or excitatory effects (depending on receptors → inhibitory: M₂ & M₄ excitatory: M₁, M₃, M₅

• labeled as muscarinic Ach receptors as they respond to muscarine & Ach

what diseases are influenced by acetylcholine?

Alzheimer’s disease (widespread loss of acetylcholine can lead to this)

where are the nuclei responsible for these neurotransmitters’ pathways?

brain stem

serotonin (5-HT → serotonergic system)

• associated with happiness (influences mood)

role: sleep, digestion, sexual desire, nausea, bone health & repair

where are serotonin cell bodies found?

brain stem (raphe nuclei)

what is serotonin’s function attributable to?

diverse array of 5-HT receptors (19 different types!)

• 18 are metabotropic receptors, 1 is ionotropic

  • alters cell function/chemistry in the long term

where does serotonin mostly project to in the brain?

fibers are seen widely thoughout the CNS

drug’s effect on serotonergic (5-HT) system

• many drugs used to treat mood disorders target the 5-HT system

  • monoamine oxidase inhibitors (MAOI) & selective serotonin reuptake inhibitors (SSRIs)

  • allows for more serotonin to be in the synapse

• hallucinogenic & stimulatory drugs (LSD, MDMA/molly/ecstasy, meth) flood the brain with serotonin, and diminishes serotonin transporters

• prolonged use → detrimental effects

glutamate

• the brain’s major excitatory signal

• most abundant neurotransmitter

• responsible for more than 90% of synaptic connections in human CNS

role: affects variety of behaviors & drives, regulates CNS, arousal, learning & memory

• binds to NMDA receptors

where is glutamate found in the brain?

EVERYWHERE!

NMDA receptors

ligand & voltage-gated

• fully active when gated by a combination of voltage (-30 mV)

• removes Mg²⁺ ion & ligands like glutamate bind

• blocked by Mg²⁺ ions, becomes more depolarized (+) until Mg²⁺ leaves → then glutamate comes in & allows Ca²⁺ to enter (which allows neurotransmitters to be produced)

ligand

neurotransmitters, hormones, or drugs that bind to an intended receptor

• endogenous agonist

GABA

• brain’s major inhibitory neurotransmitter system

• expressed in ~50% of all brain tissue

• has its effects over this system by binding to 2 different types of GABAergic receptors

role: assists with memory, cognitive function, decision-making, anxiety, sleep, developmental role in fine tuning the prefrontal cortex

• synchronizes pyramidal cells (lack of GABA neurons → cognitive dysfunction)

→ target for alcohol

GABA receptors (2 types)

ionotropic: GABA-A, GABA-C

metabotropic: GABA-B

where is GABA found in the brain?

EVERYWHERE!

agonists

receptor

• endogenous: naturally occurring

• exogenous: comes from an outside source

antagonists

receptor blocker

• exogenous: comes from outside source (like some drugs)

how do ligands, receptor agonists, and antagonists look in the brain?

ligands: endogenous agonist

• ligand gate is open when certain transmitter binds

receptor agonist: exogenous agonist

• ligand gate is open when certain drug binds

antagonist

• ligand gate is closed when antagonist blocks receptor

diagnosing drug abuse disorders

• manual of mental disorders: DSM-V

  • hardly mentions anything about the brain, mostly talks about behaviors/cravings)

  • drug addiction: substance use disorder

  • categorical diagnostic tool

lethal dose 50 (LD₅₀)

median dose required for lethal toxicity of a substance (death in 50% of population)

• every chemical has a lethal dose (H₂O > NaCl > THC > cocaine > meth > heroin > fentanyl

• dose per body weight (mg/kg)

toxic dose 50 (TD₅₀)

dose that produces a specified toxic effect in 50% of the population

• identify specific toxic effect (i.e respiratory depression with opioids: ~0.1 mg/kg)

effective dose 50 (ED₅₀)

dose that produces a specific effect in 50% of the population

• i.e pain relief

how do we decide the utility of a certain drug?

compare effective dose to either toxic dose OR lethal dose

• asks: how useful/helpful is this drug versus how risky/toxic/dangerous it is?

• in this figure, drug B would be recommended over drug A (effective dose 50 compares to lethal dose 50 at 0%)

intravenous self-administration

reinforcing strength of a drug is examined by allowing an animal to perform an action (i.e lever press) in order to receive a drug via a catheter

• catheter hooked up to syringe which administers drug when animal exerts certain behavior/action (pressing lever)

• can see if the animal wants the drug/gets addicted to it

dose-response

depicts the magnitude of a response from an animal in response to drug exposure

• can see the “sweet spot” of how reinforcing a drug is (is it too reinforcing, not enough?)

microdialysis

sampling technique to measure analyte concentrations (endogenous/natural molecules i.e dopamine release) in cerebral fluid

• can identify what chemicals are released in response to drugs

• place dialysis probe in the brain (i.e nucleus accumbens) which brings fluid in & out for analysis → i.e how much dopamine is in the fluid?

• dialysis membrane keeps fluid from entering brain, but allows certain chemicals (like dopamine) to “hitch a ride” out through probe

calcium imaging

image individual neurons as rats self-administer drug

PET imaging

image whole brain to determine difference in groups with history of substance use disorders

• those with substance use disorders have dimmer brains in PET image

incentive sensitization

conditioning of motivational signals to drug-associated cues & drugs themselves

drug withdrawal & homeostatic disruption (allostatic model)

reward deficit & stress systems

stimulants

psychoactive drugs that can alter mental/physical capacity

• leads to enhanced arousal, locomotion, alertness, wakefulness, etc.

• ex) caffeine, nicotine, cocaine, methamphetamine

depressants

drugs that include sedatives & tranquilizers & can slow brain activity

• ex) alcohol, cannabis, opioids (morphine, heroin, etc.)

hallucinogens

psychoactive substance that can cause disruptions in perception & hallucinations

• ex) LSD

stimulants: caffeine

• a stimulant

• exogneous (unnatural) neuromoderator that antagonizes/blocks the effect of adenosine receptors

• reduces inhibition of catecholamines (like dopamine) that adenosine mediates

  • results in more catecholamines like dopamine

how does caffeine work?

it structurally resembles adenosine which binds to the adenosine receptors

• instead of activating receptors, caffeine blocks them (antagonist)

• exogneous antagonist

stimulants: nicotine

• originates from tobacco

• increases heart rate, blood pressure, hydrochloric acid secretion in stomach, & bowel activity

• Ach receptor agonist

  • binds to nicotinic Ach receptors

• rewarding effects: mediated by receptors in VTA nuclear accumbens circuit (reward & addictive circuit)

stimulants: cocaine

• comes from leaves from coco shrub

• alleviates hunger, promotes endurance, enhances sense of well-being

• fast-acting, but high doesn’t last long (quickly metabolizes), highly addictive

• purified extract can be used as an anesthetic

• increases catecholamine (dopamine) stimulation

• blocks dopamine transporter receptors (DAT)

  • DAT antagonist → more dopamine in synapse

stimulants: methamphetamine

• methamphetamine & amphetamine are synthetic stimulants that resemble catecholamine structure

• causes release of neurotransmitters, even in the absence of an action potential

• short-term effects: euphoria, alertness, stamina

• repeated exposure → long-lasting deficits in concentrations of striatal dopamine & its metabolites, tyrosine hydroxylase activity & dopamine transporter binding sites

• dopamine, noradrenaline, & serotonin receptor agonist

• causes more dopamine release → dampens dopamine system

• “meth mites”: sensation of bugs crawling in skin

stimulants: amphetamine

• less dramatic than meth; ADHD medication

depressants: alcohol

has 2 different effects on GABA (inhibitory neurotransmitter)

1. acute rewarding euphoric effects (generally happens earlier in drunkenness)

• leads to more dopamine release; blocks GABA release

• prolonged use: substantial brain damage

2. reduced executive function (generally happens later; more sloppy drunk)

• increases duration of Cl^- channels opening → hyperpolarizes cell (more negative; inhibits)

• consequences: poor decision-making, aggression, loss of motor control

• more of an agonist, as it opens chloride channels

★ alcohol reduces amount of gray matter (neurons) in brain

★ astrophy: lateral ventricles increase in size (replaces where brain tissue was)

depressants: cannabis

marijuana has main effect from THC (tetrahydrocannabinol)

• binds to cannabinoid receptors

  • CB1 and CB2: G-protein-coupled receptors (metabotropic)

  • pre-synaptic heteroreceptors

• cannabinoid system (natural in body)

depressants: cannabinoid system (natural in body)

produces anandamide, which binds to CB1 receptor

• binding to CB1 inhibits GABA release

  • THC also does this

• less GABA → more DSI (depolarization-induced suppression of inhibition)

• CB1 and CB2 receptors could be on glutamate terminals

  • would stop further glutamate release

  • DSE (depolarization-induced suppression of excitation)

depressants: opiates

• opium is extracted from poppy seeds

• contains morphine (effective painkiller)

• morphine & heroin: related & are both highly addictive

• synthetic opioids (like fentanyl): dangerous due to extreme potency

  • leading cause of overdose deaths

• euphoric effect on user

depressants: opioid system

• 3 opioid receptors:

  • mu (μ) → most dangerous

  • kappa (κ)

  • delta (δ)

• drugs override this system & bind to receptors

• exogneous agonist on μ opioid receptors

hallucinogens: LSD & shrooms

• LSD: artificial hallucinogen that affects the serotonergic system

• shrooms (psylocibin): naturally occuring psychedelic that mainly activates serotonin 5-HT2A receptors

• increased brain-derived neurotropic factor (BDNF) activity → critical for brain development; “feeds” neurons & tells them how to connect)

• these drugs stimulate BDNF activity to manipulate neuronal activity

  • can have problematic long-term effects, but can have positive anti-depressant effects in lower dosages

hallucinogens: LSD & shrooms

• alters perception of the world

• affects cortical later 5 glutamatergic pyramidal neurons

• does not have a withdrawal → does not impact addiction as much

fetal brain development

• sperm & egg fuse together to create a zygote with 23 maternal chromosomes & 23 paternal chromosomes → 46 total

• at 2+ weeks, 3 major subdivisions of the brain can be identified (forebrain, midbrain, hindbrain)

• develops quickly

neurogenesis: progenitor cells

line the inner suface of neural tube (goes through mitosis)

neurogenesis: progeny cells

biological cell that eventually may leave the cell it originated from in mitosis, & may differentiate into a specific type of cell

neurogenesis

production of nerve cells critical to brain development

• cells of the neural tube divide through mitosis to create progeny cells → brain expands out

• divide in the ventricular zone & drops of progeny cells in marginal zone

• continually creating new cells

detecting neurogenesis

nucleic acid tagged with label injected at specific life stages

• later, when you see labeled cells you know when they were born

• new neurons are generated throughout lifespan (mostly in early development)

migration

neurons in developing nervous system must migrate

• cells move along radial glial cells (like a ladder)

• new neurons make their way up to these guide cells, migrating along radial glial fiber

migration drawing

differentiation

once cell arrives at its new destination, it begins to develop into a certain type of cell (glutamatergic, GABAergic, pyramidal neuron, dopamine-expressing, glial, etc.)

• cells acquire distinct characteristics like neurons

differentiation: autonomous cells

develop into specific type of cell independently on any neighboring cells (“know” genetically what they’re supposed to be)

differentiation: neural environment

some cells respond to protein release by other cells, which “tell” them what cells they’ll become

• sense the environment

process outgrowth

growth of axons & dendrites

• most extensive change in early life (abundant axon/dendrite growth)

• requires growth cones (that contain filopodia), which are attracted to or repelled by different types of molecules

cell adhesion molecules

proteins found on surface of cell that guides migration/axonal pathfinding

• chemoattractants

• chemorepellents

chemoattractants

filopodia on growth cone → target cells

chemorepellents

filopodia → away from target cells

result of process outgrowth

synaptogensis: new synapses are generated/formed

apoptosis

neuronal cell death

• programmed death to allow the brain to work appropriately & ensure proper tissue development

• prevents brains from being too large for skull

• genetic interference with ephrin signaling alters brain size by regulating apoptosis

what determines whether a particular cell will die or not?

• depends on its interaction & competition with other target structures

• neurons that receive sufficient chemicals from target structures will survive (will not undergo apoptosis)

• due to release of neurotropic factors into the cell

what signals are needed for cells to survive?

neurotrophins

• this process works when different neurotrophic factors are released by different target cells

• neurons that can take up neurotrophic factors are able to survive

• neurotrophic factors regulate gene expression within cell

synapse rearrangement

refines synaptic connections

• just like neurons, some synapses that form early are eliminated later

• results in thinning of gray matter in cortex (caudal → rostral)

• high intelligence: correlated with a greater rate of synaptic remodeling throughout adolescence