Week 7 PSY1BNA

Monoamine Neurotransmitters

• There are two main classes of monoamine neurotransmitters: Catecholamines and Indoleamines.
• Catecholamines include dopamine, epinephrine, and norepinephrine.
• Indoleamines include melatonin and serotonin.

Dopaminergic Pathways in the Brain

• Dopamine (DA) is found in neurons in the mesostriatal pathway and mesolimbocortical pathway.
• The mesostriatal pathway originates in the midbrain, specifically the substantia nigra, and innervates the striatum.
• This pathway is important in motor control and neuronal loss is a cause of Parkinson's disease.
• The mesolimbocortical DA pathway originates in the midbrain, specifically the ventral tegmental area (VTA), and projects to the limbic system and cortex.
• DA in this pathway is involved in reward, reinforcement, and learning; abnormalities are associated with schizophrenia.

Noradrenergic Pathways in the Brain

• Norepinephrine (NE) is released from two main clusters in the brainstem: Locus coeruleus (pons) and Lateral tegmental system (midbrain).
• NE is also known as noradrenaline, and cells producing it are noradrenergic.
• Noradrenergic fibers from the locus coeruleus project broadly.
• The CNS has four subtypes of NE receptors, all of which are metabotropic.
• NE systems modulate processes including mood, arousal, and sexual behavior.

Criteria for Neurotransmitters

• Chemicals released onto target cells meet the following criteria:
  • Substance exists in presynaptic axon terminals.
  • Substance is synthesized in presynaptic cells.
  • Substance is released when action potentials reach axon terminals.
  • Receptors for the substance exist on postsynaptic membrane.
  • When experimentally applied, substance produces changes in postsynaptic cells.
  • Blocking substance release prevents changes in postsynaptic cell.

Types of Neurotransmitters

• Many chemical neurotransmitters have been identified, including:
  • Amine neurotransmitters: acetylcholine, dopamine, serotonin.
  • Amino acid neurotransmitters: GABA, glutamate.
  • Peptide neurotransmitters (or neuropeptides): short chain amino acids.
  • Gas neurotransmitters: soluble gases, including nitric oxide and carbon dioxide.

Synaptic Transmission

• Co-localization, or co-release, occurs when nerve cells contain more than one type of neurotransmitter.
• The most prevalent excitatory neurotransmitters in the brain are glutamate and aspartate.
• Glutamatergic neurotransmission uses AMPA, Kainate, and NMDA receptors.
• Glutamate is associated with excitotoxicity, unlike GABA, which is inhibitory.
• Endogenous ligands are substances that the brain produces.
• Receptors on neurons may change shape (ionotropic receptors) or alter chemical reactions in the target cell (metabotropic receptors).
• A single neurotransmitter may interact with many different receptor subtypes in different parts of the brain.

Agonist and Antagonist Effects

• Ligands may be:
  • Agonists: mimic effects of another transmitter.
  • Antagonists: bind receptor without activating it.
  • Inverse agonists: bind to receptor and initiates opposite effect of usual transmitter.
• Drugs that act as either agonists, antagonists, or inverse agonists are known as competitive ligands.
• Noncompetitive ligands (or neuromodulators) bind to modulatory sites that are not part of the receptor complex that normally binds the transmitter.