Neurotransmission

Most drugs that affect behavior do so

by affecting synaptic transmission
Terminology
Agonists - drugs that act to
enhance the effects of a
particular NT
Antagonists - drugs that act to
decrease the effects of a
particular NT
Direct vs Indirect
Direct
Drug binds to receptor and mimics NT
Drug binds to and blocks receptor
Indirect
Everything else
What are some
The sequence
NT synthesized and stored in vesicles
NT released when neuron fires
NT binds to postsynaptic receptors,
producing EPSPs or IPSPs
NT reuptake or breakdown (brief effect)
Autorecepors regulate synthesis and
releasee
NEUROTRANSMITTERS
Four Major Categories
Amino acids
Amines - derived from amino acids
ACh (Acetylcholine) is the exception
Peptides - constructed from amino acids
Gases
Dales law - neuron has single NT-
applies to amino acids and amines
Co-release with peptides stored in
neurosecretory granules - an amino
acid or amine and a peptide
Small Molecule Neurotransmitters
Acetylcholine - ACh - Cholinergic
Synthesized from choline
(dietary substance-milk, eggs,
liver & peanuts) and acetyl CoA
by choline acetyltransferase
Choline availability is the rate-
limiting step
Metabolic deactivation -
acetycholinesterase- AChE
Small Molecule Neurotransmitters
Acetylcholine - ACh - Cholinergic
Nicotinic receptor
Ionotropic
Fast
neuromuscular junction
Muscarinic receptor
Metabotropic
slow
PNS

Ionotropic

Metabotropic

Small Molecule Neurotransmitters
Monoamines - MA - Monoaminergic
Catecholamines Indolamines
Dopamine - DA Serotonin - 5-HT
Dopaminergic Serotonergic
Norepinephrine - NE
Noradrenergic
Epinephrine - E
Adrenergic

Dopamine Synthesis
Tyrosine (amino acid)
Tyrosine hydroxylase
rate-limiting step
L-Dopa
Dopa decarboxylase
Dopamine (DA)
At least 5 DA receptors: D1, D2, etc
Dopamine Systems (CNS)
Nigrostriatal
Movement
Mesolimbic
Reward
Mesocortical
Short-term memories and planning

Norepinephrine Synthesis
Tyrosine (amino acid)
Tyrosine hydroxylase
L-Dopa
Dopa decarboxylase
Dopamine
Dopamine beta-hydroxylase
Norepinephrine
Alpha and beta receptor subtypes
Varicosity release
NE systems (PNS and CNS)
Pons and Medulla
Locus coeruleus
Vigilance, attention to the environment

Serotonin Synthesis
Tryptophan (amino acid) - availability is
rate-limiting step
Tryptophan hydroxylase
5-hydroxytryptophan (5-HTP)
5-HTP decarboxylase
5-hydroxytryptamine (5-HT)
At least 7 different subtypes, 5-HT
1A-1D

and 5-HT
2-4
Serotonin systems (CNS)
Most in Raphe system (brainstem)
Arousal
Sleep
Mood
Prozac (fluoxetine) blocks serotonin reuptake
Monoamines
Inactivated by reuptake
Also deactivated metabolically by
monoamine oxidase - MAO
Reserpine - makes vesicles leaky -
depletes monoamines
MAO inhibitors - increases monoamine
concentrations
Small Molecule Neurotransmitters
Amino Acids - Aminergics
Glutamate - Glu glutaminergic
synthesized from glucose
Excitatory NT in CNS
Receptors - named by agonists
AMPA - control sodium channels
NMDA - control calcium channels and
are ligand- and voltage-gated
Kainate - poorly understood

Small Molecule Neurotransmitters
Amino Acids - Aminergics
GABA GABAergic
Inhibitory NT in CNS
synthesized from glutamate by
glutamic acid decarboxylase
GABA
A
controls chloride channel
GABA
B
controls potassium channel
Glycine - inhibitory NT in spinal cord
Small Molecule Neurotransmitters
Soluble Gases
Nitric Oxide NO
synthesized from arginine by nitric oxide
synthase
Not stored in vesicles - released when
produced
Diffuses through membranes
Controls cerebral and penile
vasodilation - learning and memory
Viva Viagra!!
Other Neurotransmitter
Candidates
Carbon Monoxide - gas
Hydrogen Sulfide - gas (el stinko)
Adenosine triphosphate - ATP
Tetrahydrocannabinol THC
- endogenous ligand called anandamide