Neurotransmitters and Hormones
Agonist: drug/chemical that mimics and/or enhances the effects of a neurotransmitter
• Example: nicotine binds to an acetylcholine receptor, pretends to be it, and stimulates the
receptor
• Also if it blocks the breakdown, allowing it to be around longer
• Allows more to be released at the synapse
• Blocks reuptake
Antagonist: block the effect of the neurotransmitter
• Allows it to be broken down more quickly
• Doesn’t let the neurotransmitter bind
Synthesis of some NT’s
• Always begins with something found in the diet
• Dopamine, norepinephrine, and epinephrine share the same pathway – catecholamine
(contain a catechol group and an anime group) – add serotonin and you have the monoamines
Food for thought
• If you have a drug that’s active in the brain, it’s crossed the BBB and it’s affecting a
neurotransmitter system
→ It could be in/decreasing synthesis
→ Could be in/decreasing release
→ Alters the amount of time a neurotransmitter is in the synaptic cleft
⇒ SSRI’s: Selective Serotonin Reuptake Inhibitor; stop serotonin from being broken
down and taken up out of the synapse
→ Binds to and activates or inhibits a receptor
→ Blocks or increases neurotransmitter degradation either broken down faster or slower
Hormones Some chemicals can act as hormones AND as neurotransmitters
Hormones and their target cells
• Peptide: released from the brain, pituitary gland, pancreas, liver, etc.; going to work like NT’s
b/c receptors are usually metabotropic receptors on the surface of the cell and initiate events
in the cell
• Steroid hormones: mainly come from the gonads and adrenal glands; they can cross right
through the cell membrane and even go right into the nucleus (and effect gene transcription
directly); they affect things “hands on”
• Stimulated by a ton of different factors; internal and external factors
Pituitary gland
• Hypothalamus: controls the release of hormones; pituitary is connected by the pituitary stalk
→ anterior pituitary make hormones and release them into the bloodstream when they get
releasing hormones from the hypothalamus; thyroid stimulating hormone thyroid
stimulating hormone releasing hormone is sent here to tell to release it;
⇒ releases:
• Adrenocorticopic hormone (ACTH) ▯adrenal cortex
• Gonadotropins (follicle stimulating and lutenizing hormone – important in
menstrual cycle and ovulation)
• Prolactin ▯mammary glands
• Growth hormone (GH; somatotropin) ▯growth throughout the body
→ posterior pituitary: does not make its own hormones; releases oxytocin and vasopressin –
oxytocin: pair bonding, social attachment, contraction of the uterus, birth and
breastfeeding; vasopressin water conservation
• Negative Feedback: how to “turn off” hormone release; hypothalamus will release a releasing
hormone and sends it to A.P, A.P stimulates the hormone and then it has its effects; the
hormone sends information back to the hypothalamus and when everything is good, it turns
off the release
Study Questions 1. How are hormones transported around the body? What types of receptors do hormones use?
a. Endocrine
2. What brain region controls hormone release from the pituitary gland?
a. Hypothalamus
3. What is different between the anterior and posterior pituitary, including what hormones are
released from each lobe?
a. Anterior: makes its own hormones and releases them after getting a releasing hormone
from the hypothalamus; thyroid stimulating hormone thyroid; growth hormones; prolactin
mammary glands
b. Posterior: does not make its own hormones; only releases the hormones it’s told to;
oxytocin and vasopressin
4. What are some other glands in the body that pituitary hormones influence?
a. Pineal, parathyroid, thyroid, mammary
5. Understand the principle of negative feedback in hormone release.
a. How to “turn off” hormone release; hypothalamus will release a releasing hormone and
sends it to A.P, A.P stimulates the hormone and then it has its effects; the hormone sends information
back to the hypothalamus and when everything is good, it turns off the release
Drugs of Abuse
Drugs: facilitate or inhibit transmission at synapses
Drugs of abuse: effect on dopamine in the brain at the Nucleus Accumbens (NA)
• NA is underneath the cortex
• Dopamine comes from the ventral tegmental area (VTA) in the midbrain; their axons go to
NA and release dopamine their; reinforcement circuit – it tells the brain to do that again, that
was good
→ Some reinforcing circuit stimulating:
⇒ Sex, overeating, gambling, exercising, substance abuse, lust, video games, thrill
seeking(?), selfharm, eating disorders, alcohol • NA & dopamine
→ Animals such as rats with work hard for any type of stimulation to the NA; we use this
for research before submitting a drug to the FDA to make sure it’s not addictive; why? If
a rat is addicted to it and will work hard for it, chances are, people will too
→ fMRI in heterosexual men
⇒ looked at photos of attractive women ▯increased activity in the NA
⇒ looked at photos of attractive men ▯decrease activity in the NA
→ wanting vs. liking
⇒ reinforcer is more attached to wanting than liking; it’s not so much that the person
enjoys the drug/activity, it’s that the brain tells them that they need it or they have to
have it; this could often go against the fact that you know there will be negative
consequences
→ dopamine is not only implicated in drug abuse, but it can also be released with “natural
reinforcers”
⇒ How can we increase dopamine release in NA?
• Inhibit GABA neuron; it’s always to some extent blocking the neuron (opiates)
• Stimulate VTA dopamine neurons (nicotine)
• Block dopamine transporter (cocaine, Ritalin)
• Reverse dopamine transporter (amphetamine)
→ Stimulants
⇒ Amphetamine (AMPH), Cocaine, Ritalin (for ADHD and ADD), Ecstasy
⇒ Causes excitement
⇒ Pharmacological actions
• Increases dopamine by blocking or reversing dopamine transporter, especially in
NA
• MDMA (Ecstasy)
→ Stimulant at low doses – increases dopamine release..norepinephrine too → Stimulant at high doses – recreational
→ Psychological effects: euphoria, wellbeing, happiness, stimulation, increased energy,
extroversion, feeling close to others, increased empathy
⇒ Much of this is due to serotonin, some to oxytocin
→ Physical effects
⇒ Release of posterior pituitary hormones
• Oxytocin: “lovey dovey” aspect comes from this; hormone between mother and
child and lovers
• Vasopression: antidiuretic; tells you to retain water and drink water; they can
drink so much water that they become water intoxicated
⇒ Increased body temperature (hypothermia VERY DANGEROUS); increased blood
pressure and heart rate; pupil dilation
→ Animal studies
⇒ Adolescent exposure to MDMA and alcohol together ▯decreased number of granule
cells in hippocampul formation, increased memory impairment (rats)
⇒ Large injections of MDMA destroy serotonin and dopamine neurons
• Due to increased body temp; metabolizing excess leads to mitochondrial damage;
sometimes, neurons can recover
→ Human users
⇒ Low doses cause negative effects on brain vasculature, white matter maturation,
axonal damage
⇒ More depression, anxiety, sleep problems, memory deficits, attention problems, and
impulsiveness, even 12 years after quitting
⇒ Your brain tries to remain homeostasis and so when you do drugs, your brain tries to
compensate for them; when you stop doing the drug, your brain continues to
compensate for something for something that’s not there; that’s where a lot of
addiction comes from
Serotonin syndrome • Serotonin syndrome: too much serotonin released into body because of too much of a
serotonin agonist or because mixing drugs that all act in some capacity as serotonin agonists.
Nicotine
• Increases dopamine release in nucleus accumbens
→ Stimulates nicotinic Ach receptor on VTA neurons, thereby exciting them
→ VTA neurons project to nucleus accumbens and release dopamine
• Cells become less responsive than usual after repeated nicotine use (tolerance) other
pleasures (including nicotine itself) become less reinforcing
• Other things are reinforcing become less so when they used more and more often.
Opiates
• Examples
→ Morphine
→ Heroin
→ Methadone
• Derived from opioid poppy or chemically similar to its derivatives
• Bind to opioid receptors
• Why do you have those?? (Hint: endorphins)
• Opiate drugs
→ Bind to opioid receptors in nucleus accumbens (and elsewhere) and on GABA neurons in
VTA (GABA usually inhibits Da neurons in VTA that project to NA; inhibit the GABA
neurons = disinhibition of dopamine neurons)
→ Also work independently of Da
→ Mice w/ almost no dopamine still develop preference for places they got morphine
→ Also inhibit locus coeruleus, a hindbrain area that releases norepinephrine in response to
stressful stimuli
→ Decrease stress response and memory. → Methadone
⇒ Taken to combat opioid addiction
⇒ Similar to heroin and morphine (mu opioid agonist)
⇒ Taken as pill, so enters blood and brain slowly – no rush
⇒ Metabolized slowly – no crash
⇒ Gradual effects…more moderate withdrawal
⇒ Still highly addictive, but less dangerous than heroin or morphine
⇒ Combined with naloxone so people don’t just inject the methadone.
→ Naloxone (opioid receptor antagonist) blocks opioid effects if injected
→ Naloxone breaks down in stomach acids if taken orally, as directed.
Cannabinoids
• Marijuana (deltaTHC and other cannabinoids)
→ Receptors: CB1 and CB2 (metabotropic)
→ Ubiquitous, except for medulla – They are everywhere in the body.
→ Psychological effects : intense sensory experiences and illusion of time passing slowly
⇒ Impairment of memory and cognition (acts in hippocampus)
→ Memory tends to recover after ~4 weeks w/o drug
→ Inhibit GABA in VTA more dopamine to nucleus accumbens (like opiates, but less
potent)
→ Dissolves in body fats and leaves slowly fewer withdrawal symptoms than other drugs
→ Heavy smokers do report withdrawal symptoms after longterm use (anxiety, depression,
stomach pain, craving, loss of appetite, sleep problems
• Alcohol
→ GABA agonist → Combines w/ GABA to produce longer normal effects of GABA (opens Clchannel wider
than usual)
→ Antianxiety and intoxicating effects due to this action
→ Glutamate receptor antagonist (so depressant in this way too)
→ Also gets into membrane of cells and messes things up
→ Stimulant? NO! just decreases brain activity in some areas that are responsible for
inhibiting risky behavior.
→ Increases stimulation at both dopamine and opiate receptors, including in nucleus
accumbens
• Substance Abuse
→ Alcohol and Alcoholism
⇒ Alcoholism: continued use of alcohol despite medical or social harm, even after
having made a decision to quit or decrease drinking
⇒ Third largest health problem after heart disease and cancer.
⇒ The numbers:
• 90% of population have experienced alcohol at some time in their lives.
⇒ Type 1
• Later onset
• Gradual onset
• Fewer genetic relatives with alcoholism
• Equal quantity between men and women
• Less severe
⇒ Type 2
• Earlier onset
• More rapid onset • More genetic relatives with alcoholism
• Men outnumber women often severe
• Often associated with criminality
⇒ Genes and alcoholism
• Gene for a dopamine receptor
→ The longer version of the gene makes less sensitive receptors
→ People with this version experience stronger cravings for more alcohol after
one drink.
→ Gene for enzyme that breaks down dopamine
• COMT breaks down all catecholamines (Da, NE, Epi)
• One version of gene makes enzyme that is more active than the other
• People with more active enzyme break down dopamine faster – les reinforcement
from things that increase dopamine
• Tend to be more impulsive with alcohol and other things (choose immediate
rewards instead of bigger ones later
⇒ Risk Factors for alcoholism
• Sons of alcoholics have specific traits relating to 1. How alcohol affects them and
2. Their neuroanatomy…
• Less than average intoxication after drinking moderate amount of alcohol (these
people have a 60% chance of developing alcoholism)
→ Report feeling less drunk, have less body sway, fewer changes in EEG
• Decreases stress more than for other people
• Smaller amygdala on right
→ Amygdala responds to emotions, especially negative emotions; the right
hemisphere (in general, including amygdala) is more responsive to emotional
stimuli
→ Substance Abuse ⇒ Start taking a drug: Dopamine in NA is reinforcing…continue taking the drug
⇒ Develop tolerance: a decrease in the effectiveness of a drug that is administered
repeatedly; you take a little bit, and you need more for an effect; you take a little bit
more, and you need more to feel an effect; so on and so forth
⇒ Need more of the drug to get same effect
⇒ Other pleasurable things become less reinforcing
⇒ Withdrawal:
• Opposite effect of what drug was doing for you
• Because body tried to compensate for having drug in system (find homeostasis;
this was basis of tolerance)…now no drug in system but still have compensatory
mechanism in place
• Craving
→ Because the drug decreases
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