Neurotransmitters, Pharmacokinetics, and Dopamine: Study Notes for Psychology

Proof of Concept: Neurotransmitter (NT)

Introduction to Neurotransmitters

Neurotransmitters (NTs) are chemical messengers that transmit signals across synapses in the nervous system. Their discovery and study have been fundamental in understanding how neurons communicate and regulate physiological processes.

• Early Evidence: Action potentials were known, but the existence of NTs was initially unknown.

• Otto Loewi's Experiment: Demonstrated that communication between neurons is not only electrical but also chemical.

• Hypothesis: Neurons release chemical messengers.

• Example: Vagus nerve stimulation slows heart rate by releasing acetylcholine (ACh); another branch releases norepinephrine (NE) to increase heart rate.

Categories of Classical NTs

Types of Neurotransmitters

Neurotransmitters are classified based on their chemical structure and function.

• Acetylcholine (ACh)

• Monoamines:

  • Catecholamines: Dopamine (DA), Norepinephrine (NE), Epinephrine (E)

  • Indolamines: Serotonin (5-HT), Melatonin

• Amino Acids: Glutamate, GABA, Glycine

• Endocannabinoid NTs: Anandamide (AEA), 2-Arachidonoylglycerol (2-AG)

• Peptide Neuromodulators: Endorphins

Drugs and the Body

Pharmacokinetics

Pharmacokinetics describes what the body does to a drug, including absorption, distribution, metabolism, and excretion.

• Absorption: Route of administration affects how quickly and efficiently a drug enters the bloodstream.

• Distribution: How the drug spreads throughout the body.

• Metabolism: How the drug is broken down, often by the liver.

• Excretion: How the drug is eliminated, usually via urine.

Pharmacodynamics

Pharmacodynamics refers to what the drug does to the body, especially the brain and behavior, and the mechanisms of action.

• Blood-Brain Barrier: Determines if a drug can affect the central nervous system by crossing into the brain.

Pharmacokinetics Concepts

• Routes of Administration: Oral, subcutaneous (SC), intramuscular (IM), intraperitoneal (IP), intravenous (IV)

• Bioavailability: Fraction of the drug that reaches systemic circulation and is available to have an effect.

• First Pass Metabolism: Drugs taken orally are partially metabolized by the liver before reaching systemic circulation.

• Elimination Kinetics: Describes how quickly a drug is removed from the body (e.g., half-life).

Principles of Drug Action

Key Principles

• Multiple Effects: Drugs can have effects on both central and peripheral systems.

• Receptor Specificity: Drugs act on specific receptors, affecting selectivity and side effects.

• Agonists and Antagonists:

  • Agonist: Facilitates or mimics the action of a neurotransmitter.

  • Antagonist: Inhibits or blocks the action of a neurotransmitter.

Acetylcholine (ACh)

Overview and Functions

Acetylcholine is a key neurotransmitter involved in both the peripheral and central nervous systems.

• Peripheral Nervous System (PNS): ACh is the main NT at the neuromuscular junction, causing muscle contraction.

• Autonomic Nervous System: ACh acts on the vagus nerve to slow heart rate.

• Central Nervous System (CNS): Involved in arousal, learning, memory, and sleep-wake cycles.

Synthesis

• Choline (from diet) + Acetyl CoA (from metabolism) → Acetylcholine (ACh)

Receptors

• Nicotinic Cholinergic Receptors (nAChR): Ionotropic, fast-acting, found at neuromuscular junctions and in the brain.

• Muscarinic Cholinergic Receptors (mAChR): Metabotropic, slower, found in the brain and involved in REM sleep and other CNS functions.

Drugs Affecting ACh

• Agonists: Nicotine (nAChR), Muscarine (mAChR)

• Antagonists: Curare (nAChR), Atropine (mAChR)

• Enzyme Inhibitors: Physostigmine, neostigmine (inhibit acetylcholinesterase, increasing ACh levels)

• Botulinum Toxin: Blocks ACh release, causing paralysis

Dopamine (DA): Functions and Pathways

Major Dopaminergic Pathways

• Nigrostriatal Pathway: Substantia nigra to striatum; involved in movement regulation.

• Mesolimbic Pathway: Ventral tegmental area (VTA) to nucleus accumbens; involved in reward and reinforcement.

• Mesocortical Pathway: VTA to prefrontal cortex; involved in cognition and executive function.

• Tuberoinfundibular Pathway: Hypothalamus to pituitary; regulates hormone secretion.

Synthesis and Metabolism of Catecholamines

• Precursor: Tyrosine (from diet)

• Enzymes: Tyrosine hydroxylase → DOPA decarboxylase → Dopamine

• Further Conversion: Dopamine can be converted to norepinephrine and epinephrine

• Metabolism: Broken down by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)

Dopamine Receptors

• Five main subtypes: D1–D5

• D1 and D5 are excitatory; D2–D4 are inhibitory

Dopamine and Psychopathology

• Schizophrenia: Associated with excess DA activity, especially in the mesolimbic pathway

• Parkinson's Disease: Loss of DA neurons in the substantia nigra

• Drug Abuse: Many abused drugs increase DA release or block reuptake (e.g., cocaine, amphetamines)

Drugs Affecting Dopamine

• Agonists: Amphetamines, cocaine (increase DA release or block reuptake)

• Antagonists: Antipsychotics (e.g., haloperidol, thorazine) block DA receptors

Pharmacological Manipulation of NTs

Mechanisms

• Agonists: Increase NT action (e.g., L-DOPA for Parkinson's)

• Antagonists: Block NT action (e.g., antipsychotics for schizophrenia)

• Enzyme Inhibitors: Prevent breakdown of NTs (e.g., MAO inhibitors for depression)

• Reuptake Inhibitors: Block reabsorption of NTs, increasing their availability (e.g., SSRIs for serotonin)

Summary Table: Major Neurotransmitters and Functions

Neurotransmitter	Main Functions	Key Drugs/Disorders
Acetylcholine (ACh)	Muscle contraction, learning, memory	Botulinum toxin, Alzheimer's disease
Dopamine (DA)	Movement, reward, motivation	Parkinson's, schizophrenia, drug abuse
Serotonin (5-HT)	Mood, sleep, appetite	SSRIs, depression
Norepinephrine (NE)	Alertness, arousal	ADHD, depression
GABA	Main inhibitory NT	Benzodiazepines, anxiety
Glutamate	Main excitatory NT	Epilepsy, neurotoxicity

Additional info:

• Some details about the blood-brain barrier, elimination kinetics, and specific drug mechanisms were expanded for clarity and completeness.

• Table entries and some explanations were inferred and expanded based on standard academic knowledge in neuropsychology and pharmacology.