Biopsych Exam 3- Neuropharmacology

Otto Loewi’s Experiment

Frog heart experiment: Heart 1: vagus nerve attached → stimulation slows heart. Heart 2: in same solution → slows when fluid from Heart 1 added. Conclusion: neurons use chemical signals (not just electrical) to communicate.

Endogenous Substances

Made within the body (e.g., neurotransmitters released from presynaptic neurons).

Exogenous Substances

Introduced from outside the body (e.g., Tylenol, caffeine).

Presynaptic Neuron

Sends signal; releases neurotransmitter.

Postsynaptic Neuron

Receives signal via receptors.

Co-localization of Neurotransmitters

Some neurons release more than one neurotransmitter; can influence multiple types of signaling at once.

What is Glutamate?

Major excitatory neurotransmitter; most predominant in brain.

Where is Glutamate sent from?

Sent from everywhere → everywhere.

What is Glutamate critical for?

Memory and excitatory signaling.

What does an oversupply of Glutamate cause?

Migraines and seizures.

What is GABA?

Major inhibitory neurotransmitter; amino acid NT.

Where is GABA sent from?

Sent from everywhere → everywhere.

What is GABA critical for? 

Inhibiting neuronal firing and calming neural activity.

What does an undersupply of GABA cause?

Seizures, tremors, and insomnia.

What is acetylcholine (ACh)?

Neurotransmitter involved in learning, memory, and motor control.

Where is Acetylcholine (ACh) sent from? 

Basal forebrain → cortex, amygdala, hippocampus, skeletal muscles, and PNS.

What is Acetylcholine (ACh) critical for?

CNS: learning & memory; PNS: motor control & parasympathetic activity.

What does a malfunction of Acetylcholine (ACh) cause?

Alzheimer’s disease; antagonists like Botox paralyze muscles.

What is Dopamine (DA)?

Neurotransmitter involved in movement, learning, reward, attention, and emotion.

Where is Dopamine (DA) sent from?

Midbrain (Ventral Tegmental Area & Substantia Nigra) → cortex, basal ganglia, nucleus accumbens.

What is Dopamine (DA) critical for?

Reward processing, movement control, and motivation.

What does an oversupply of Dopamine (DA) cause?

Schizophrenia

What does an undersupply of Dopamine (DA) cause?

Parkinson’s disease.

What is Serotonin (5-HT)?

Neurotransmitter involved in mood, vision, sexual behavior, anxiety, hunger, sleep, and arousal.

Where is Serotonin (5-HT) sent from?

Midbrain (Raphe Nuclei) → forebrain.

What is Serotonin (5-HT) critical for?

Regulating mood, vision, sleep, and behavior.

What does an undersupply of Serotonin (5-HT) cause?

Depression; psychedelics can alter vision.

What is Norepinephrine (NE)?

Neurotransmitter involved in alertness, mood, and sexual behavior.

Where is Norepinephrine (NE) sent from?

Locus coeruleus & lateral tegmental area → cortex, limbic system, thalamic nuclei.

What is Norepinephrine (NE) critical for?

Alertness, attention, and mood regulation.

What does an undersupply of Norepinephrine (NE) cause?

Depressed mood.

What are opioid peptides?

Neurotransmitters involved in pain perception, reward, and maternal care.

Where are opioid peptides sent from?

Everywhere → everywhere, especially spinal cord & PAG.

What are opioid peptides critical for?

Pain perception, thrill, sexual behavior, hunger, and maternal care.

What does an oversupply of opioid peptides via drugs cause?

Suppressed critical functions (breathing, heart rate).

Reuptake

NT molecules reabsorbed by presynaptic neuron.

Transporters

Membrane proteins that move NTs back for reuse.

Enzymes (Degradation)

Break down neurotransmitters.

Ionotropic Receptors

Ligand-gated ion channels; fast response. A receptor protein containing an ion channel that opens when the receptor is bound by an agonist

Metabotropic Receptors

Second-messenger systems; slower, modulatory.

Excitatory Synapse (EPSP)

Depolarizes postsynaptic neuron → more likely to fire.

Inhibitory Synapse (IPSP)

Hyperpolarizes postsynaptic neuron → less likely to fire.

Classical Neurotransmitter Criteria

Synthesized in presynaptic neuron & stored in terminals;

Released by action potential;

Recognized by postsynaptic receptors;

Causes change in postsynaptic cell;

Blocking release disrupts signaling.

Retrograde Neurotransmitters

Released by postsynaptic neuron → acts on presynaptic neuron.

Competitive vs. Non-Competitive

Compete for receptor vs. modify activity without direct binding.

Agonist

Increases neurotransmitter effects

Antagonist

Decreases neurotransmitter effects

Partial agonist

A drug that, when bound to a receptor, has less effect than the endogenous ligand would.

Ligand

A substance that binds to receptor molecules, such as a neurotransmitter or drug that binds to postsynaptic receptors

Bioavailability

The ability of a drug or other substance to be absorbed and used by the body.

Biotransformation

When the body changes a drug into another form (metabolite) using enzymes, which can act differently than the original drug.

Binding affinity

Strength of binding.

Efficacy

Effectiveness of the drug.

Dose-response curve (DRC)

Relationship between drug dose & effect.

ED50

Effective dose where we see effect with at least 50% of our sample

LD50

Lethal dose- 50% of sample has died

Therapeutic index

Range between effective dose (ED50) and lethal dose (LD50).

Blood-brain-barrier

Prevents large molecules from entering CNS.

Routes of drug administration

Oral, intravenous, inhalation, subcutaneous, intramuscular, transdermal.

Metabolic tolerance

Body eliminates drug faster.

Functional tolerance

Target tissue alters sensitivity (up- or down-regulation).

Conditioned tolerance

Environment influences tolerance.

Cross tolerance

Tolerance generalizes to similar drugs.

What is drug action at the production stage?

How much neurotransmitter the neuron can make.

How does an agonist affect production?

Acts as a precursor → increases neurotransmitter production.

How does an antagonist affect production?

Blocks synthesis → reduces neurotransmitter production.

What is drug action at the release stage?

How much neurotransmitter is released into the synapse.

How does an agonist affect release?

Increases release (often by increasing Ca²⁺ influx).

How does an antagonist affect release?

Blocks release → less neurotransmitter reaches postsynaptic neuron.

What is drug action at the clearance stage?

How quickly neurotransmitters are removed from the synapse.

How does an agonist affect clearance?

Blocks reuptake or degradation → neurotransmitter stays longer in the synapse.

How does an antagonist affect clearance?

Speeds up removal → neurotransmitter is cleared faster, reducing its effect.

What is drug action at the receptor stage?

How the drug interacts with the postsynaptic receptor.

How does an agonist affect receptors?

Activates the receptor → mimics or enhances neurotransmitter effects.

How does an antagonist affect receptors?

Blocks the receptor → prevents neurotransmitter from acting.

What is the difference between competitive and non-competitive receptor drugs?

Competitive → competes for the same binding site; Non-competitive → changes receptor activity without blocking the site.

What drugs affect the GABA system?

Alcohol, benzodiazepines, and barbiturates. They act as CNS depressants that enhance GABA’s inhibitory effects.

What drugs affect the opioid system?

Morphine and heroin bind to opioid receptors, producing pain relief and euphoria; highly addictive. The PAG is involved in pain modulation.

What drugs affect the serotonin system?

LSD acts as a 5-HT2A agonist; MDMA reverses serotonin transporters, flooding the synapse with serotonin.

What drugs affect the endocannabinoid system?

THC stimulates CB1 receptors; CBD modulates THC’s effects.

What drugs affect stimulant systems?

Nicotine increases ACh; cocaine and amphetamines increase dopamine; caffeine blocks adenosine; methamphetamine strongly boosts dopamine release.

What are examples of depressants?

Alcohol, GHB, barbiturates, and benzodiazepines — they slow the central nervous system.

What are examples of stimulants?

Caffeine, nicotine, amphetamines, and cocaine — they increase alertness and energy.

What are examples of hallucinogens (entheogens)?

LSD, psilocybin (mushrooms), MDMA, and ketamine — they alter perception, mood, and thought.

What are neuroleptics (antipsychotics)?

Dopamine antagonists; typical ones block D2 receptors, while atypical ones affect multiple receptor types.

What are SSRIs, SNRIs, and tricyclics used for?

They treat depression and anxiety by blocking serotonin, norepinephrine, or dopamine reuptake.

What are MAOIs?

Drugs that block monoamine oxidase, increasing levels of serotonin, norepinephrine, and dopamine.

How do drugs affect the medulla?

Trigger nausea and vomiting by activating the CTZ (chemoreceptor trigger zone).

How do drugs affect the cerebellum?

Impair movement and coordination; affected by alcohol and cannabinoids.

How do drugs affect the basal ganglia?

Influence movement control; affected by dopamine-related drugs.

How do drugs affect the cortex?

Alter cognition and perception; affected by hallucinogens.

How do drugs affect the hypothalamus?

Change appetite and body regulation; affected by THC.

How do drugs affect the hippocampus?

Disrupt memory and stress regulation; affected by alcohol and cannabinoids.

How do drugs affect the spinal cord?

Reduce pain sensation; affected by opioids.

What are the main models of drug addiction?

Moral model, disease model, physical dependence model, and positive reward model (most dominant).

Nucleus Accumbens

Reward center; receives DA from VTA → reinforced behavior.

Insula

May mediate conscious urges/cravings.