Chapter 1

PSYCHOPHARMACOLOGY: DRUGS OF PHARMACOTHERAPY AND ADDICTION

• Author: James D. Calvert, Ph.D.

Chapter 1: Neurobiology

Neurons and Glial Cells

• Neurons (Nerve Cells):

  • Estimated 86 billion in the human brain.

  • Composed of 85 billion glial cells (support cells).

  • Approximately 100 trillion synapses.

  • Unlike most body cells, neurons are generally not replaced (exceptions noted in the hippocampus for some regeneration).

Neuron Anatomy

• Key structures include:

  • Dendrites: Receive signals from other neurons.

  • Axon: Transmits impulses away from cell body.

  • Nucleus: Contains genetic material.

  • Axon Terminal: Release neurotransmitters into synapses.

  • Myelin: Insulating layer around axons (produced by Schwann cells in the peripheral nervous system).

  • Node of Ranvier: Gaps in myelin sheath facilitating faster impulse transmission.

  • Soma: The cell body containing the nucleus.

Types of Neurons

• Multipolar Neurons: Common in the brain and spinal cord.

• Unipolar Neurons: Typically sensory neurons which transmit information from the body to the brain.

• Bipolar Neurons: Found in sensory organs (e.g., eyes).

• Pseudounipolar Neurons: A single process that branches into two, common in sensory neurons.

Action Potential

• Neuronal Impulses consist of:

  • Resting state (polarized): Negative internal charge.

  • Depolarized state (excited): Sodium ions (Na+) influx causes a positive internal charge.

  • Followed by Repolarization: Potassium ions (K+) exit neuron returning to resting state.

Glial Cells and Neurotransmitters

• Functions of Glial Cells:

  • Insulate and support neurons.

  • Prevent neurotransmitter (NT) spread to adjacent synapses.

  • Absorb and recycle NT for neuron’s reuse.

  • Can release NT themselves (e.g., glutamate).

  • Act against Dale’s principle (neurons release only one type of NT).

• Main Types of Glial Cells:

  • Oligodendrocytes: Myelin production in CNS.

  • Astrocytes: Connect neurons to blood supply, regulate neurotransmitter recycling.

  • Microglia: CNS immune defense, eliminate plaques/infections.

  • Ependymal Cells: Line brain ventricles and circulate cerebrospinal fluid.

  • Radial Glia: Guide new neurons during development.

  • Schwann Cells: Myelin production in peripheral neurons.

Synapses

• Types of Chemical Synapses:

  • Axodendritic: Dendrites as targets.

  • Axosomatic: Cell bodies as targets.

  • Axoaxonic: Axons as targets.

• Synapses facilitate NT release influencing signal transmission:

  • Electrical synapses allow rapid communication—important in specific contexts like heart regulation.

Neurotransmitter Dynamics

• Receptor Mechanisms:

  • Ionic Receptors: Ligand-gated (e.g., rapid response via ion channels).

  • Metabolic Receptors: G-protein coupled (most psychiatric drugs target these).

• Autoreceptors: Monitor NT levels and adjust release accordingly.

• Reuptake Transporters: Remove NT from synapse for recycling or elimination.

• NT Metabolism includes:

  • Breakdown by enzymes (e.g., MAO, COMT, AChE).

  • Simple diffusion or removal by microglia.

Key Neurotransmitters and Their Functions

• Glutamate: Primary excitatory neurotransmitter (e.g., NMDA and AMPA receptors).

• GABA: Primary inhibitory NT; subtypes include GABAA (ionic) and GABAB (metabotropic). Drugs affecting GABA are key in treating anxiety disorders.

• Norepinephrine (NE): Involved in arousal, reward, and numerous physiological functions. It acts on alpha (α) and beta (β) adrenergic receptors.

• Dopamine (DA): Plays roles in reward, addiction, motor functions, and cognition. Distinct receptor families (D1, D2) have different distributions and effects.

• Serotonin (5-HT): Involved in mood regulation, appetite, and reward pathways, with various receptor types influencing its diverse roles.

• Acetylcholine (ACh): Involved in CNS functions (memory, attention) and operates through nicotinic and muscarinic receptor types.

Neuroanatomy and Brain Functions

Lobes of the Brain

• Frontal Lobe: Reasoning, planning, impulse control, motor functions.

• Parietal Lobe: Sensation, perception, spatial orientation.

• Temporal Lobe: Auditory processing, memory formation.

• Occipital Lobe: Visual processing.

Executive Functions

• Governed by prefrontal areas:

  • Go System: Maintains attention and directs behaviors.

  • Stop System: Inhibits inappropriate responses.

Limbic System and Emotion

• Structures involved in emotion regulation and memory (e.g., amygdala, hippocampus).

• Implicated in anxiety disorders and impulse control conditions.

Basal Ganglia

• Key structures for motor control and reward processing (e.g., Nucleus Accumbens).

Autonomic Nervous System (ANS)

• Regulates involuntary functions:

  • Parasympathetic Division: Restores energy, conserves resources.

  • Sympathetic Division: Triggers fight or flight response, increases heart rate/breathing.

Neuronal Response to Trauma/Stress

• HPA Axis and SNS activation leads to hormonal (e.g., adrenaline) responses to stressors.