Wednesday, 2 March 2016

Neurotransmitters

BRIEF REVIEW OF NEUROTRANSMITTERS

Acetylcholine (ACh)
1. Neurotransmitter at nerve-muscle connections for all voluntary muscles of the body
2. Also many of the involuntary (autonomic) nervous system synapses
3. Despite long history, the exact role of ACh in the brain unclear
4. Cholinergic neurons concentrated in the RAS and basal forebrain
5. Significant role in Alzheimer disease
6. Dementia in general associated with decreased ACh concentrations in amygdala, hippocampus, and temporal neocortex
7. Associated with erections in males
8. Muscarinic and nicotinic receptors
9. In the corpus striatum, ACh circuits are in equilibrium with dopamine neurons.

Norepinephrine (NE)
1. One of the catecholamine neurotransmitters
2. Transmitter of the sympathetic nerves of the autonomic nervous system, which mediate emergency respons
a. Acceleration of the heart
b. Dilatation of the bronchi
c. Elevation of blood pressure
3. Implicated in altering attention, perception, and mood
4. Key pathway: locus ceruleus in upper pons
5. Implicated in monoamine hypothesis of affective disorders:
a. Depletion of NE leads to depression
b. Excess of NE (and serotonin) leads to mania
c. Based on two observations:
1. Reserpine depletes NE and causes depression.
11. Antidepressant drugs block NE re-uptake, thus increasing the amount of NE available postsynaptically.
6. Receptors:
a. Alpha-I: sympathetic ( vasoconstriction)
b. Alpha-2: on cell bodies of presynaptic neurons, inhibit NE release
c. Beta-1: excitatory for heart, lungs, brain
d. Beta-2: excitatory for vasodilatation and bronchodilatation

Dopamine
1. The other catecholamine neurotransmitter
2. Synthesized from the amino acid tyrosine
3. D2 receptors most important
4. D1 and D5 stimulate G-protein and increase cAMP and excitation
5. D2, D3, and D 4 inhibit G-protein and decrease cAMP and excitation
6. Three pathways of known psychiatric importance:
a. Nigrostriatal pathway • Blockade leads to tremors, muscle rigidity, bradykinesia b. Meso-limbic-cortico pathway • Blockade leads to reduction of psychotic symptoms
c. Tuberoinfundibular system • Blockade leads to increases in prolactin (Dop = PIF)

Serotonin (5-hydroxytryptamine, 5-HT)
1. The transmitter of a discrete group of neurons that all have cell bodies located in the raphe nuclei of the brain stem
2. Changes in the activity of serotonin neurons are related to the actions of psychedelic drugs.
3. Involved in the therapeutic mechanism of action of antidepressant treatments (most are 5-HT re-uptake inhibitors; a few new ones are 5-HT agonists)
4. Has inhibitory influence; linked to impulse control
5. Low 5-HT =low impulse control
6. Has role in regulation of mood, sleep, sexual activity, aggression, anxiety, motor activity, cognitive function, appetite, circadian rhythms, neuroendocrine function, and body temperature

Glutamic Acid
1. One of the major amino acids in general metabolism and protein synthesis, also a neurotransmitter
2. Stimulates neurons to fire; principal excitatory neurotransmitter in the brain 3. The neurotransmitter of the major neuronal pathway that connects the cerebral cortex and the corpus striatum
4. Also the transmitter of the granule cells, which are the most numerous neurons in the cerebellum
5. Evidence that glutamic acid is the principal neurotransmitter of the vi-sual pathway
6. May have a role in producing schizophrenic symptoms
7. Reason for PCP symptoms (antagonist ofNMDA glutamate receptors)
8. Glutamate agonists produce seizures in animal studies

Enkephalins
1. Composed of two peptides, each containing five amino acids
2. Normally occurring substances that act on opiate receptors, mimicking the effects of opiates
3. Neurons are localized to areas of the brain that regulate functions influenced by opiate drugs.

Substance P
1. Peptide containing 11 amino acids
2. A major transmitter of sensory neurons that convey pain sensation from the periphery, especially the skin, into the spinal cord
3. Also found in numerous brain regions
4. Opiates relieve pain in part by blocking the release of substance P.
5. New class of antidepressant medications being tested to work on substance P

Gamma Amino-butyric Acid (GABA)
1. One of the amino-acid transmitters in the brain
2. Occurs almost exclusively in the brain
3. Reduces the firing of neurons; principle inhibitory neurotransmitter in the brain 4. The transmitter present at 25 to 40% of all synapses in the brain
5. Quantitatively, the predominant transmitter in the brain
6. Associated with anxiety, cannabis, benzodiazepines

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