PHYSIOLOGICAL PSYCHOLOGY (FINALS)

• GABA (Gamma-aminobutyric Acid) Neurotransmitter
• GABA PATHWAYS:

  • Gaba is the main inhibitory neurotransmitter in the central nervous system
  • Projects to the different parts of the brain
  • 50% of the inhibitory synapses in the brain are GABA-mediated
• SYNSTHESIS OF GABA:

  • Produced from its precursor molecule: Glutamic Acid also known as Glutamate.
  • Glutamate is further broken down by the enzyme Glutamic Acid Decarboxylase.
• EFFECTS OF DRUGS IN THE SYNTHESIS OF GABA:

  • Allylglycine is an ANTAGONIST that inactivates the enzyme GAD
  • The drugs has LITTLE THERAPEUTIC USE because low levels of GABA would result to seizures.
• A decreased number of GABA would potentially harm the human brain. As the main inhibitory neurotransmitter in the brain, it mediates the excitatory neurotransmitters from firing uncontrollably which would manifest itself as seizure.
• BINDING OF GABA:

  • GABA has two types of receptors namely GABA-A and GABA-B
  • GABA-A receptors are ionotropic which means that it opens Chloride channels. When Cl- ions enter, it HYPERPOLARIZES the neuron hence inhibiting action potentials to occur. They are concentrated in limbic system and retina.
  • GABA-B receptors are metaBotropic which means they open Potassium channels. When K+ LEAVES the neuron, the neuron HYPERPOLARIZES again making the probability of action potentials to occur LEAST LIKELY. Found mostly in Thalamic system and cerebral cortex
• GABA-A RECEPTORS:

  • Have 5 different binding sites.
  • PRIMARY SITE: intended for GABA
  • Direct agonist of the primary site: Muscimol
  • Direct antagonist of the primary site: Bicuculline
• • SECOND SITE: intended for a class of drugs called BENZODIAZEPINES
  • Benzodiazepines include drugs that help in REDUCING SYMPTOMS of anxiety, seizures, and produce MUSCLE RELAXATION. These drugs include DIAZEPAM (valium) and ALPRAZOLAM (xanax)
  • THIRD SITE: binds with BARBITURATES
  • Older class of sedatives and anti-anxiety drugs

  Alcohols binds with an as-yet-unknown site in GABA-a

  Another site binds with steroids (including ones used to produce anesthesia)
• DRUGS THAT PROMOTE GABA-A RECEPTORS::

  • INDIRECT AGONIST
  • Benzodiazepine
  • Is an anxiolytic useful in treating symptoms of anxiety disorders
  • Drugs under benzodiazepine like ZOLPIDEM (ambien) and ESZOPICLONE (lunesta) are effective sleep medications.
  • Barbiturates
  • Not considered as first-line therapeutic intervention due to their sedative effects
• DRUGS THAT INHIBIT GABA-A RECEPTORS:

  • INDIRECT ANTAGONIST
  • Picrotoxin inhibits activities of GABA-A receptors
  • Can cause seizures (in high doses)
• INACTIVATION AND REUPTAKE OF GABA:

  • GABA can either be re-absorbed back to the pre-synaptic neuron as a GABA again ready for re-usage.
  • GABA is removed by GABA transporters. Its antagonist is TIAGABINE (gabitril) which is used to increase number of GABA and reduce seizures.
  • GABA is inactivated in the GLIAL cell and is broken down by the help of GABA Aminotransferase as glutamate and re-absorbed back to the pre-synaptic neuron.
  • GABA Aminotransferase is blocked by its antagonist called VIGABATRIN (sabril) and hence enhancing availability of GABA in the synapse decreasing likelihood of seizures
• ROLE OF GABA IN HUMAN BEHAVIOR:

  • GABA works to WEAKEN or SLOW DOWN signals.
  • GABA helps in alleviating symptoms of ANXIETY, FEAR, and STRESS because of its INHIBITORY NATURE which significantly slows down signal transmission
• GLUTAMATE

  • Major Excitatory Neurotransmitter
• GLUTAMATE PATHWAYS:

  • Glutamatergic Pathways
  • Found throughout the brain, hence no specific pathways
• SYNTHESIS OF GLUTAMATE:

  • Precursor molecule: Glutamine
  • Enzyme: Glutaminase
• BINDING OF GLUTAMATE:

  • Four Major Types of Glutamate Receptors
  • Three are Ionotropic and one is metabotropic
  • Ionotropic: NMDA (N-methyl-D-Aspartate), AMPA (a-amino-3-hydroxy- 5-methyl-4-isoxazoleproprionic acid, and Kainate
• AMPA Receptor:

  • Most common glutamate receptor
  • Opens Na+ channels thus depolarizing the neuron making an action potential more likely to occur.
• Kainate receptor:

  • Opens Na+ ion channels which makes the neuron depolarize making an action potential more likely to happen.
• NMDA Receptor:

  • Opens Na+ and Ca+ ion channels
  • Contains at least SIX binding sites (four located on the exterior of the receptor and two located within ion channel)
  • Entry of calcium serves as 2nd messenger binding and activating many enzymes in the cell.
• INACTIVATION AND REUPTAKE OF GLUTAMATE:

  • Glutamate is removed by Excitatory Amino Acid Transporters (EAAT)
  • Glutamate is broken down by Glutamine Synthase into Glutamine
  • Failure to remove glutamate from synapse can result to Glutamate Excitotoxicity.
• • GLUTAMATE EXCITOTOXICITY
  • a cell death mechanism
  • involved in Stroke and ALS (Amyotrophic Lateral Sclerosis; Lou Gehrig's Disease)
  • Riluzole (Rilutek) is a drug antagonist that reduces glutamate signaling and reduces glutamate vesicle docking in the membrane to release NT.
• ROLE OF GLUTAMATE IN HUMAN BEHAVIOR:

  • Helps in prenatal and childhood brain development
  • Majorly implicated on Long-term Potentiation
• LONG-TERM POTENTIATION:

  • NMDA is involved here
  • process by which new information/skill is retained for later use
  • strengthens connections between neurons after neurogenesis halts
  • Decreased glutamate excitation results in difficulty concentrating or mental exhaustion
• BEHAVIORS LINKED TO GLUTAMATE:

  • Learning
  • Memory