Neurotransmitters and Drug Actions

NEUROTRANSMITTERS AND DRUG ACTION

Neurotransmitter Storage and Release

• Neurotransmitter Function: Stored in synaptic vesicles; transported to presynaptic membrane for release.
• Transporter Molecules: Responsible for filling vesicles and reuptake of neurotransmitters into terminal buttons.
  • Blocking Agents: Some drugs can block transporter molecules, preventing filling of vesicles, acting as antagonists.
  • Release Mechanism: Drugs can either inhibit vesicle fusion (antagonists) or facilitate neurotransmitter release (agonists).

Effects on Receptors

• Function of Receptors: Critical sites for drug action in the nervous system (both presynaptic and postsynaptic).
• Postsynaptic Receptors:
  • Agonists: Mimic neurotransmitter and activate receptors (e.g., binding to the active site).
  • Antagonists: Bind receptor without activating (occupy binding site, preventing neurotransmitter action).
  • Examples:
  • Direct agonists activate receptors and influence ion channels directly.
  • Receptor blockers prevent normal ligand binding, negatively affecting synaptic transmission.

Key Terms in Neurotransmission

• Agonist: Enhances neurotransmitter effects on postsynaptic cells.
• Antagonist: Inhibits neurotransmitter effects on postsynaptic cells.
• Direct Agonist: Activates the receptor directly.
• Receptor Blocker: Occupies binding site without activating the receptor.
• Indirect Agonist/Antagonist: Acts on different binding sites and modifies receptor action without blocking the primary binding site.

Neurotransmitter Reuptake and Destruction

• Termination of Effects: Occurs via reuptake or enzymatic destruction of neurotransmitter.
  • Role of Drugs: Can block either reuptake (by binding with transporter molecules) or inhibit enzymatic destruction (e.g., inhibitors of acetylcholinesterase).
  • Outcome: Prolonged neurotransmitter presence in synaptic cleft, enhancing postsynaptic effects (acting as agonists).

Drug Action Sites

• Processes Interfered with by Drugs:
  • Synthesis of neurotransmitters.
  • Storage in vesicles.
  • Release mechanisms.
  • Receptor interactions (both presynaptic and postsynaptic).
  • Reuptake processes.
  • Enzymatic destruction.
• Agonist vs Antagonist Action: Affects various neurotransmitter pathways differently.

Types of Neurotransmitters

Major Neurotransmitters:

• Acetylcholine (ACh): Involved in muscular movement, CNS functions, REM sleep; has ionotropic (nicotinic) and metabotropic (muscarinic) receptors.
• Monoamines: Include dopamine, norepinephrine, serotonin, have similarities in molecular structures.
  • Dopamine: Key role in movement, attention; implicated in addiction pathways.
  • Major Pathways:
    • Mesolimbic Pathway: Reward and pleasure.
    • Mesocortical Pathway: Cognition and decision-making.
    • Nigrostriatal Pathway: Motor control (linked to Parkinson's disease).
    • Tuberoinfundibular Pathway: Regulates hormone release.
• Glutamate: Principal excitatory neurotransmitter; operates through various receptor types (NMDA, AMPA).
• GABA: Principal inhibitory neurotransmitter; regulates neuronal excitability, two receptor types (GABA(a) and GABA(b)).
• Glycine: Inhibitory neurotransmitter in spinal cord.
• Peptides: Chains of amino acids; include endogenous opioids (e.g., endorphins).
• Adenosine: Neuromodulator involved with sleep and blood flow.
• Nitric Oxide: Soluble gas; acts as a signaling molecule and is involved in numerous physiological processes.

Drugs and Their Effects

• Acetylcholine:
  • Botulinum Toxin: Blocks ACh release.
  • Nicotine: Agonist for nicotinic receptors.
• Dopamine:
  • L-DOPA: Precursor, acts as an agonist.
• Norepinephrine:
  • MDMA: Agonist for norepinephrine.
• Serotonin:
  • Fluoxetine (Prozac): Inhibits reuptake, acting as an agonist.
• GABA:
  • Benzodiazepines: Indirect agonists, enhance GABA(a) receptor activity.
• Adenosine:
  • Caffeine: Antagonist for adenosine receptors.

Conclusion

• Understanding neurotransmitter action and drug effects is crucial in physiological psychology, highlighting the complex interactions that underlie brain function and influence behavior.