Action Potentials (AP) release neurotransmitters (NTs) in the synapse

Body must be able to produce the chemical (endogenous)

Must be produced by the neuron When a neuron is stimulated, a chemical

is releasedChemical must act upon a receptor

to produce an effect

Major excitatory NT

Excess of glutamate can lead to hyperexcitation seizure

NMDA Receptor

AMPA and Kainate Receptor

Major inhibitory NT

Deficit in GABA may lead to lack of inhibition seizure (hyperexcitability or excitotoxicity)

GABA

Open chloride channels

Produces more profound sedative effects

Anti-convulsant

GABAA Receptor Agonist

Benzodiazepene agonist

Cerebellum has a lot of GABAa receptors

Rats have been tested using the rotorod test

Dopamine agonist leads to increase in pleasure, addiction, aggression

Dorsal vs. Ventral Pathways

D1 vs. D2 Receptors D1- Postsynaptic D2- Autoreceptor

Binds DA transporter and blocks DA reuptake, which increases synaptic DA

Produces motor activation, reward, motivational, hedonic effects

Sensitization

Causes DA transporter to release DA, blocks reuptake

Non-selective, so causes release of DA, NE, and 5HT

Used for ADHD

Found in locus coeruleus (LC)

Involved in attention and arousal, sympathetic nervous system activation

α2 vs. β receptors α2- Autoreceptor β- Blocks NE

Found in the raphe nucleus of midbrain

Deficit of 5HT can lead to depression

REM sleep deprivation can be used to treat severe depression short term

5HT1a

Predominant autoreceptor that works through GPCR

5HT2a

Predominant postsynaptic receptor that works through GPCR

LSD (5HT2a agonist) produces sensory disturbances, hedonic and panic effects, and hallucinations

Prozac, Zoloft

Many SSRIs have bad withdrawal symptoms like severe vertigo and nausea

Many antidepressants have increased suicide at onset primarily in younger population (within 2-3 weeks of drug use)

Found in the nucleus basalis and projects to the cortex

Important for cognition and muscle contraction

Acetyl CoA + Choline

Choline + Acetate

Acetylcholine + Coenzyme A

Choline transferase

Acetylcholineesterase (ACE)

Ligand gated ion channel Found in the peripheral NS

(skeletal muscle)

Nicotinic antagonist (curare) causes muscle paralysis @ NMJ

Nicotinic agonist increases muscle tension and causes tremors

Inhibitory receptor

Muscarinic agonist produces pupil constriction, diarrhea, and increase in GI activity (activates parasympathetic activity)

Muscarinic antagonist (scopolamine) used to treat diarrhea (block parasympathetic activity)

Inhibits ACh release

Toxin is very stable

Causes paralysis of the diaphragm

Have their own GPCR, meaning that there are lots of receptors

Coexist with small molecule NT

Endorphins/enkephalins

Corticotropin Release Factor (CRF)

Secreted by neurons in hypothalamus to stimulate ACTH release from anterior pituitary

Amygdala PAG hypothalamus activates sympathetic NS

CRF antagonist is anxiolytic

CRF is elevated in most depressed individuals

Endogenous cannabinoids (anandamide and 2AG)

Cannot be packaged, synthesized and released on demand

Cannabinoid receptor CB1 CB1 agonist

Orexogenic, rewarding, affects timing behavior, analgesic

Important second messenger

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