Lecture 2: Synaptic Function and Psychopharmacology

Synaptic Transmission

• Excitatory Post-Synaptic Potentials (EPSPs):

  • Depolarize the post-synaptic membrane.

  • Increase the likelihood of an action potential.

  • Example: Glutamate typically causes EPSPs.

• Inhibitory Post-Synaptic Potentials (IPSPs):

  • Hyperpolarize the post-synaptic membrane.

  • Decrease the likelihood of an action potential.

  • Example: GABA typically causes IPSPs.

• Temporal Summation:

  • Multiple signals are received from the same neuron in rapid succession.

  • The combined effect can trigger an action potential if the threshold is reached.

• Spatial Summation:

  • Signals from multiple neurons are received simultaneously.

  • The combined effect can trigger an action potential if the threshold is reached.

Neurotransmitters (NT)

• Acetylcholine (ACh):

  • Found at neuromuscular junctions and in the hippocampus.

  • Generally excitatory.

  • Important for memory formation.

  • Depletion is linked to Alzheimer's Disease.

• Noradrenaline (NA) / Norepinephrine (NE):

  • Involved in the fight/flight response.

  • Affects arousal, sleep, and mood.

  • Drugs like cocaine and amphetamines affect NA levels.

• Dopamine (DA):

  • Involved in movement, memory, and motivation.

  • Different pathways: Nigrostriatal (movement), Mesocorticolimbic (memory and motivation).

  • Lower levels are associated with Parkinson's Disease.

• 5-Hydroxytryptamine (Serotonin or 5-HT):

  • Involved in temperature regulation, sleep, feeding, and sensory perception.

  • Linked to depression, anxiety, migraine, and eating disorders.

  • Derived from tryptophan.

• Gamma-Aminobutyric Acid (GABA):

  • Inhibitory neurotransmitter.

  • Involved in regulating neuronal excitability throughout the nervous system.

  • Its effects are enhanced by sedatives like benzodiazepines, barbiturates, and alcohol.

Drugs and Synaptic Function

• Agonists:

  • Drugs that bind to receptors and mimic the action of a neurotransmitter.

  • Example: Nicotine is an agonist for acetylcholine receptors.

• Antagonists:

  • Drugs that bind to receptors and inhibit the action of a neurotransmitter.

  • Example: Naloxone is an antagonist for opioid receptors.

• Inverse Agonists:

  • Bind to the same receptor as an agonist but induce the opposite effect.

Psychoactive Drugs and Addiction

• Adaptation:

  • Up-Regulation: Increase in receptor numbers in response to a decrease in neurotransmitter levels.

  • Down-Regulation: Decrease in receptor numbers in response to an increase in neurotransmitter levels.

• Psychoactive Drugs:

  • Substances that affect the brain and change mood, perception, or consciousness.

  • Examples include stimulants (e.g., cocaine), depressants (e.g., alcohol), and hallucinogens (e.g., LSD).

Parkinson’s Disease

• Symptoms: Tremors, rigidity, poor balance, shuffling gait, cognitive effects, mood changes.

• Cause: Degeneration of the substantia nigra and dopaminergic neurons.

• Treatment:

  • L-Dopa (precursor to dopamine).

  • DA agonists (e.g., pergolide).

  • MAO-B inhibitors.

Alzheimer’s Disease

• Pathology: Degeneration of ACh-secreting neurons in the basal nucleus.

• Treatment:

  • Choline (ACh precursor) is relatively ineffective.

  • ACh cannot cross the blood-brain barrier and is rapidly degraded by AChE.