Catecholamines:

– dopamine
– norepinephrine
– epinephrine
Indolamines:
- serotonin

= Produces either an IPSP or EPSP depending on the postsynaptic receptor
= Involved with movement, attention, learning, and reinforcement

= Implicated in Parkinson’s disease and Schizophrenia

Tyrosine -amino acid taken from our diet

Tyrosine Hydroxytase
l-dopa -precursor for dopamine

DOPA Decarboxylase
Dopamine -precursor for norepinephrine

Dopamin b-Hyroxylase

Norepinephrine

VMAT2 -a transporter on the vesicle

–vesicular monoamine transporter protein
•Blocked by reserpine
–Sedates animals, depressed humans
–Carlsson showed that resperine depletion of dopamine could be reversed by l-dopa
Led to the catecholamine theory of depression

Dopaminergic Pathways

know origin and termination & behavioral effects

Multiple receptor classes
– D1 –D5
– There are subtypes of each one of these also
• D1 and D2 most common
• D1 is postynaptic
• D2 is presynaptic and postsynaptic
– D3 and D4 are subtypes of D2 and found in limbic areas

–D5 is a subtype of D1
• Stimulates adenylate cyclase activity
• High in limbic areas

•L-DOPA
–Agonist, facilitates synthesis
•Cocaine
–Agonist, blocks reuptake
•AMPH
– Agonist, multiple effects, reuptake and release
• Reserpine

– Antagonist, inhibits vesicle storage
• Clozapine
– Antagonist, blocks D4 receptor

• Chlorpromazine
– Antagonist, blocks D2 receptor
• Haloperidole
– D2 antagonist, produces catalepsy

– Phenothiazines, thioxanthenes, butryrophenones

– (Phenos) Effectiveness correlated with action on DA
– Block postsynaptic receptors, extrapyramidal side effects
– Other classes increase turnover of DA

• Found in neurons of the ANS
• NE = noradrenaline
• Epinephrine = adrenaline
• NE is involved in attention, motor learning, hunger/eating, and affect
• Released from axonal varicosities, not terminal buttons “volume transmission”

• Vigilance

Norepinephrine pathways

know origin and termination & behavioral effects

Role of Norepinephrine on vigilance

Acetylcholine (ACh)

• Primarily involved in cognition, learning and memory

•Also thought to modulate sensory reception

–Behavioral arousal

–Attention

–Energy conservation

–Mood

–REM activity

Acetyl CoA+ choline⇔Ach + CoA

•ChAT

–enzyme involved in the synthesis of Ach

–Also used as a marker

•Cholineis the rate limiting factor

–Transported from the blood

•Synthesis in presynapticterminals

•Cholinesterasesbreak down AChAcetylcholinesterase(AChE)

–Enzyme in neural tissue

–Very efficient enzyme

•5000 molecules/sec

          –Antagonists

•Reversible–physostigmine

•Irreversible –organophosphates–sarin

Reversible AchEinhibitors

–Used to treat Alzheimer’s

–Tacrine(Cognex) and Donepezil(Aricept)

•Pseudo-irreversible AChEinhibitor

–Rivastigmine –form covalent bond with AChEtemporarily inhibiting it, as the bond is gradually broken down enzyme activity returns

–Gives 10 hrs of inhibition

Nicotinic

Muscarinic

ACh receptor

–Stimulated by muscarine, blocked by atropine

–5 classes (M1-M5)

–Metabotrophic

•Sometimes can produce a hyperpolarization

–Open or close K+, Ca++, Cl-

–Neocortex, hippocampus, MFB have high level

ACh receptor

–Stimulated by nicotine, blocked by curare

–Muscle (α,β,γ,δ)

–Neural (α,β)

–NMJ and other areas

•Also occurs presynapticallyand enhances release

–Open or close K+, Ca++, Cl-

•Neuromuscular junction

•Dorsal lateral pons, REM sleep

•Basal forebrain-nuc. bas.-cortex, learning

•Medial septalarea, modulation of the hippo, memory formation

•Striatal interneurons

Muscarinicreceptors control a lot of peripheral effects

–Contraction in cardiac muscle is lessened

–Contraction is smooth muscle is enhanced

–Mediate crying, salivation, sweating

–Cholinergic antagonist produce dry mouth

Parasympathomimetic agents

–Mimics the sympathetic activation of agonist

–Pilocarpine, amanita (a deadly mushroom)

–Sweating, crying, salivation, pinpoint pupils, smooth muscle contration

•Parasympatholytic

–Inhibit the action of the parasympathetic system

–Antagonist action

–Atropine, scopolamine

•Deadly nightshade

–An alkaloid plant that has paraympatholytic effects

•5-HT

•Found in midbrain nuclei and brainstem

–Main pathway originates in the raphenucleus

–Projections to cerebellum, hippocampus, amygdala, neocortex

•Involved in regulation of mood, eating, sleep, arousal, pain, and dreaming

•Also released from axonal varicosities

Tryptophan to 5-Htp to 5-HT

Found in midbrain nuclei and brainstem

–Main pathway originates in the raphe nucleus

–Projections to cerebellum, hippocampus, amygdala, neocortex

• Involved in regulation of mood, eating, sleep, arousal, pain, and dreaming

Fenfluramine

-agoniststimulates release; diet drug

LSD

- agoniststimulates 5-HT_2A

PCPA

- antagonist inhibits tryptophan hydroxylase

• Glutamic acid

• aspartic acid

–Synthesized in the breakdown of glucose
–Re-uptake by astrocytes
–Major excitatory nt in the CNS
–Role in cognitive function, motor function, plasticity and neurotoxicity
–Contained in all neurons and glial cells
•Also used in protein synthesis and cellular metabolism

–Distribution
•Hippocampus, cortex, spinal cord

•NMDA
      –Ca channel, also NaNon-NMDA receptors
•AMPA amino-3-hydroxy-5-methyl-4-isoxazloe proprionic acid
        –Na channel
        –Most common fast receptor
•Kainate
         –Na channel
•Metabotrophic
          –8 different receptors mGluR1-mGluR8
          –Can act like autoreceptors

•Glycine
–Required for channel opening
•Mg
–Regulates Ca flow
•Polyamine
–Agonist
•Zn
–Antagonist
•PCP
–Inverse agonist

For receptor to work glutamate and glycine have to be bound and the membrane depolarized

GABA (γ-aminobutyric acid)

Glycine

glutamic acid ⇔GABA

GAD (glutamic acid decarboxylase) is responsible for removing a carboxyl group from glutamic acid and forming GABA.

-GABA-T
–In GABAergic neurons and astrocytes