Drugs

Course Introduction

  • Course Title: NEU 101: Drugs

  • Date: Thursday, October 2, 2025

  • Reminder to discuss differences between ions and neurotransmitters.

Announcements & Reminders

  • Review of Quiz #1 is available during office hours.

    • Office hours:

    • Wednesday: Zoom

    • Thursday: Zoom or in-person

    • Sign up 24 hours in advance for appointment slots.

    • Drop-in hours on Tuesday from 3:00-4:00 PM.

  • Quiz #2 is scheduled for Tuesday, October 7.

    • Study effectively by engaging in productive activities beyond passive review.

    • Prepare to arrange sequences correctly.

    • Learning is compared to physical workouts.

    • Questions and comments are welcomed.

Unconventional Neurotransmitters: Endocannabinoids

  • Definition: Endocannabinoids are substances similar to THC, the psychoactive component of marijuana.

  • Characteristics:

    • Actively being researched to discover various types.

    • Synthesized immediately prior to release from the cell membrane's fatty compounds.

    • Released from dendrites and soma and do not follow the action potential protocol.

    • Receptors for endocannabinoids are primarily located on the axons of presynaptic cells.

    • Exhibit indirect (modulatory) effects on neurotransmission, affecting several functions such as:

    • Pain management

    • Memory processing

    • Mood regulation

    • Immune responses

    • Stress management

Pharmacology Overview

  • Definition: Pharmacology is the study of interactions between chemicals and living organisms.

  • Related Fields:

    • Psychopharmacology/Neuropharmacology: Focuses on how chemicals influence mind and brain.

    • Toxicology: The study of harmful drug and toxin effects.

  • Key Concepts:

    • Pharmacodynamics: Examines how drugs impact the body, including receptor binding.

    • Pharmacokinetics: Investigates how the body processes drugs (absorption, metabolism, excretion).

Receptors and Binding Mechanisms

Receptor Structure

  • Receptor proteins feature multiple subunits, allowing various interactions with drugs and neurotransmitters.

Specific Sites on Receptors

  • Binding sites include:

    • Picrotoxin site

    • Site for barbiturates

    • GABA site

    • Chloride channel

    • Steroid site

    • Benzodiazepine site

    • Glutamate recognition site

    • Polyamine site

    • Zn²⁺ site

    • Cytoplasmic side sites, including PCP and glycine

    • Influences from Ca²⁺ and Mg²⁺ at various sites.

Binding Theories

  • Lock & Key Hypothesis (1890s): Suggests neurotransmitters act as keys fitting into receptor locks.

  • Induced-Fit Hypothesis (1950s): Proposes that receptors and neurotransmitters adapt upon binding, causing shape changes in the receptor.

Nature of Drugs

  • Drugs themselves are not inherently good or bad; the effects depend on their usage.

Disclaimer on Mechanisms of Action

  • Most psychoactive substances have multiple mechanisms of action.

  • The complexity of individual drugs’ pharmacodynamics is acknowledged.

  • Course recommendation: "Your Brain on Drugs" (NEU 307) for in-depth analysis of receptors and synapses.

Reward Pathways and Drug Use

  • Drugs that feel pleasurable often activate the dopamine "reward" pathway:

    • Key brain structures:

    • Prefrontal cortex

    • Nucleus accumbens

    • Ventral tegmental area

  • Example: Lab rats will engage in behaviors (e.g., pressing a lever) to stimulate this pathway leading to behavioral changes.

Drug Effects on Neurotransmitters

Agonists and Antagonists

  • Agonist: Mimics neurotransmitter effects (e.g., enhances glutamate excitation or GABA inhibition).

  • Antagonist: Reduces neurotransmitter effects (e.g., blocks glutamate or GABA actions).

  • Types:

    • Direct acting: binds to receptors.

    • Indirect acting: influences release or reuptake without direct receptor interaction.

Direct Agonism & Antagonism

  • Direct Agonists: Bind to receptors, invoking the same physiological responses as the neurotransmitter.

    • Example:

    • Nicotine acts as a direct agonist at nicotinic acetylcholine receptors.

  • Direct Antagonists: Physically block receptors, preventing normal neurotransmitter function.

    • Example:

    • Curare blocks nicotinic receptors, inhibiting muscle control leading to paralysis.

Example Case Studies

Direct Effects of Acetylcholine

  • Direct Agonists:

    • Nicotine binds and mimics acetylcholine effects at nicotinic receptors.

    • Muscarine acts similarly at muscarinic receptors.

  • Direct Antagonists:

    • Curare (nicotinic antagonist) results in paralysis due to blocked muscle control.

    • Atropine (muscarinic antagonist) dilates pupils and impairs memory, potentially leading to death at high doses.

Indirect Agonism & Antagonism

  • Drugs can influence neurotransmitter dynamics without binding directly:

    • Botulinum Toxin: ACh antagonist, blocks release of acetylcholine (can be fatal).

    • Black Widow Spider Venom: ACh agonist, causes excessive release, leading to possible death due to paralysis.

  • Example of Gabapentin:

    • It does not affect GABA directly but inhibits calcium channels, reducing neurotransmitter release.

Tolerance Mechanisms

  • Tolerance results from the body's efforts to maintain homeostasis after repeated drug exposure.

  • Types of tolerance:

    • Metabolic Tolerance: Changes in drug metabolism.

    • Functional Tolerance: Receptor-level changes (e.g., downregulation/upregulation).

    • Environmental Tolerance: Varies based on drug context.

Changes in Receptor Functionality

  • Downregulation: Fewer receptors occur in response to elevated transmitter levels (e.g., from agonists).

  • Upregulation: More receptors develop in response to reduced transmitter levels (e.g., from antagonists).

Conclusion

  • Understanding drug effects requires a comprehensive approach considering drug mechanisms, receptor interactions, and physiological and psychological impacts on neurotransmission and behavior.