Final

• All cells in the body contain high concentrations of various amino acids because of their crucial role in

  protein synthesis and in metabolism
• Some amino acids serve as

  precursors for NTs (eg. tyrosine/tryptophan)
• Amino acid used directly as a NT

  glutamate & aspartate
• most abundant free non-essential amino acids

  glutamate & aspartate
• are glutamate & aspartate required by diet?


  no can be readily synthesized by the body
• most prevalent excitatory AA in CNS

  Glutamate
• Glu is synthesized in

  nerve terminals of glutamatergic neurons
• Glu descending pathways


  from neocortical pyramidal cells
• Glu pathways


  several intra-hippocampal and hippocampal projection
• AMPA, Kainate, NMDA


  ionotropic, ligand-gated
• Metabotropic


  post-synaptic, G-coupled receptor, involved in synaptic plasticity
• AMPA, Kainate, NMDA agonists

  in high doses tend to produce neurotoxic effects- excitotoxicity
• AMPA, Kainate, NMDA antagonists


  often used experimentally to assess behavioural functions
• glutamate receptors and LTP


  An enduring change in communication between pre and post synaptic cells in response to salient stimulation
• NMDAR or AMPAR antagonists

  block LTP induction
• Only AMPAR antagonists


  block LTP expression
• Blocking the action of GABA or glycine can lead to


  convulsions and death
• selective marker for GABA

  GAD
• How GAD can be identified


  by immunohistochemistry
• Loss of GABA can cause

  Huntingtons disease
• GABA A ionotropic or metabotropic?

  ionotropic
• GABA A orthosteric site

  GABA
• GABA A allosteric site

  picrotoxin
• Targets orthosteric site


  Muscimol and Bicuculline
• Muscimol


  - competitive agonist

  - may induce hallucinations by inhibiting 5-HT release
• Bicuculline


  - competitive agonist

  - Potent convulsant drug
• Targets allosteric sites


  Picrotoxin & Metrazol
• Picrotoxin & Metrazol


  - noncompetitive antagonists

  - causes seizures
• Benzodiazepines


  sedative-hypnotic, anxiolytic, muscle relaxant, and anticonvulsant effects
• Benzodiazepines impair


  attention and memory
• The effects of BDZs are mediated by

  increased GABA-stimulated flow of Cl- across the cell membrane
• increased GABA-stimulated flow of Cl- across the cell membrane increases


  the rate of channel opening, therefore enhancing GABA
• In the absence of GABA


  BDZs have no effect on their own
• BDZ anatagonists


  Compete with the site, not GABA
• BDZ inverse agonists


  - Produce anxiety and seizures at larger doses

  - Decrease conductance of Cl- when GABA binds (opposite effect of agonists)
• Alcohol on GABA A

  - acts at BDZ site

  - cross tolerance
• Barbituates


  - separate allosteric binding site

  - can act is GABA isn't there
• Barbituates acting


  - at low doses like BDZs

  - at high doses, act as GABA mimetics, directly opening Cl- channels
• Lipophilic hormones are synthesized from

  cholesterol in the gonads and the adrenal cortex
• Lipophilic hormones are best known for their ability to

  regulate the transcription of specific genes in target populations