Neurotransmitters

Question 1

What are the classes of neurotransmitters, and examples of them?

Answer 1

Small molecules- ACh, amino acids, monoamines.
Peptides- Endorphins, angiotensin, substance P, CRF, oxytocin.
Dissolved gases- NO, CO
Neurosteroids- Glucocorticoids

Question 2

List the main amino acid nt’s.

Answer 2

Glutamate- Major excitatory nt in cortex and spinal cord.
GABA- Main inhibitory nt in cortex.
Glycine- Major inhibitory nt in spinal cord.

Question 3

List the division of monoamine nt’s.

Answer 3

Catecholamines- dopamine, norepi, epi.
Indolamines- Serotonin
Imidazoles- Histamine

Question 4

What are the main differences between classical and peptide nt’s?

Answer 4

Peptide can function at lower active concentrations (picomolar instead of nano to micro), have a higher potency, are synthesized more slowly, and are smaller.

Question 5

What are the divisions of ionotropic nt receptors?

Answer 5

Excitatory: NAChR’s, glutamate/aspartate receptors, 5-HT3.
Inhibitory: GABA-a, glycine receptors

Question 6

What are the divisions of metabotropic nt receptors?

Answer 6

Muscarinic cholinergic receptors, adrenergic (alpha 1&2, beta 1&2), GABA-b, DA receptors, histamine receptors, peptide receptors 5-HT receptors (1a, 1b, 1d, 2a, 2c).

Question 7

What is the basic structure of an ionotropic receptor?

Answer 7

5 subunits forming a receptor binding site and ion channel that function quickly by undergoing a conformational change permitting fast ion exchange when nt binds.

Question 8

What is the general structure of metabotropic nt receptors?

Answer 8

It is a GPCR, so 7 transmembrane regions. Activated g-protein can be Gs or Gi to activate/inhibit adenylate kinase, which can activate/inhibit PKA, which activates/inhibits phosphoprotein phosphatase activity. All of this leads to altered membrane permeability, and can have long term effects (regulation of gene expression).

Question 9

What are long term changes that occur with regard to nt’s?

Answer 9

Sensitization- Decreased nt levels result in increased receptors and response.
Desensitization- Increased nt levels resulting in reduced receptors and activity.
Plasticity- Strengthening of synaptic connections (memory formation, recovery of function).

Question 10

What are the main ways termination of nt effects occurs?

Answer 10

Degradation/recycling by specific enzymes (ACh, MAO, COMT), reuptake by high adding to transmembrane transporters (glutamate, GABA, glycine, serotonin, DA, norepi), diffusion away from the site (neuropeptides).

Question 11

What are the ways drugs affecting nt’s presynaptically function?

Answer 11

1. Block reuptake (antidepressants)
2. Alter precursor availability (L-DOPA for Parkinson’s)
3. Inhibit nt synthesis
4. Inhibit nt storage
5. Alter nt release rates (amphetamines)
6. Give rise to presynaptic regulation via autoreceptors or heteroreceptors.

Question 12

How do drugs affecting nt function postsynaptically function?

Answer 12

1. Agonists bind to receptors to produce a response that the nt would.
2. Antagonists bind the receptor an nt does to decrease or inhibit the response.
3. Confers receptor adaptation, where repeated doses of drug lead to long term sensitization or desensitization.

Question 13

What is the third way drugs can affect nt function?

Answer 13

They inhibit enzymes that degrade the nt’s, thus increases the amount present (ex. AChE inhibitors).

Question 14

Describe the mechanism with which ACh is produced.

Answer 14

In the septal nuclei, Nucleus Basalis of Meynert (degenerates in Alzheimer’s), striatum (degenerates in Huntington’s), and dorsal tagmental area of pontine reticular formation (plays a role in consciousness).

Question 15

Describe where DA is produced.

Answer 15

The substantia nigra (degenerates in Parkinson’s), ventral tagmental area (involved in reward and schizophrenia), and accurate nucleus of the hypothalamus (regulates prolactin release).

Question 16

Where is norepi created?

Answer 16

In the locus coeruleus (involved in attention, arousal, and pain control).

Question 17

Where is serotonin produced?

Answer 17

The raphe nuclei (associated with depression, insomnia, mania, pain control).

Question 18

What is an autoreceptor?

Answer 18

An alternate receptor for the released nt on the presynaptic neuron that monitor the amount released and inhibit further release once a threshold has been passed.

Question 19

What is a heteroreceptor?

Answer 19

A presynaptic receptor for an nt other than the one released that when bound to a different nt released from a different neuron, shut off the presynaptic neuron nt release.

Question 20

What is the treatment strategy for Alzheimer’s?

Answer 20

Increasing the amount of ACh present in the synapse by AChE inhibitors, resulting in released ACh acting longer in the synapse. This combats the loss of cholinergic neurons.

Question 21

What is the treatment strategy for Parkinson’s?

Answer 21

Administering L-DOPA DA precursor, as it can cross the BBB unlike DA.
Also Carbidopa that acts as a false substrate for peripheral AAAD so natural L-DOPA isn’t affected and can diffuse through the BBB to be metabolized by central AAAD to make DA

Question 22

What is the treatment strategy for anxiety?

Answer 22

Stimulation of GABA-a receptors via drugs that bind to their benzodiazepine site and increase their chloride-mediated hyperpolarization and thus inhibitory action.
Drugs that do this are Valium and Librium for which anti anxiety effects do not show tolerance, but relaxation and sleep aid effects do.

Question 23

How was depression originally treated?

Answer 23

1. Monoamine oxidase inhibitors that block the activity of MAO, and allow monoamine (NE, 5-HT, and DA) levels to rise in synapses.
2. TCAs to block the reuptake of monoamines, also increasing their levels in the synapse.

Question 24

What is new treatment strategy for depression?

Answer 24

Selective Serotonin Reuptake Inhibitors, SSRIs such as Prozac, that have fewer side effects than TCAs. They still act on NE and DA transporters, but more so on 5-HT transporters (though depression mainly stems from serotonin imbalance, which then affects other monoamine levels).

Question 25

What is the treatment strategy for schizophrenia?

Answer 25

As it is though to be an imbalance in the dopaminergic symptom, drugs like Haldol block the DA receptor and present overstimulation of it which is causal in schizophrenia.
Note drugs like haldol modulate positive symptoms (hallucinations) better than negative (withdrawal, lack of affect).

Question 26

For Haldol, in what systems are improvements and side effects seen in?

Answer 26

Improvements- Mesocorticolimbic system.

Side effects- Nigrostriatal system and tuberoinfundibular system.

Question 27

What type of drugs have the highest abuse potential?

Answer 27

Those that affect the dopamine system, such as cocaine, amphetamine, and methamphetamine.

Question 28

What is the effect of cocaine, short and long term?

Answer 28

Short- Blocking DA reuptake transporter. Note high affinity and fast onset can make a single dose permanently alter the DA receptor system.
Long- Sensitization, plasticity, and neurotoxic effects.

Question 29

Where are the dopaminergic neurons indicated in addiction present?

Answer 29

In the ventral tagmental area, which then project to the nucleus acumbens of the medial forebrain bundle of the Limbic system. This results in modulation or prefrontal cortex activity and pleasurable experience.

Question 30

How to treatments for cocaine addiction generally function?

Answer 30

They prevent the drug’s action on pleasure circuits by:

1. Introducing an Ab against cocaine that capture it before it reaches its site of effect.
2. Drugs used to break the addiction cycle, but these are not well understood.

Question 31

What is the effect of heroin?

Answer 31

A disinhibition activity in the VTA by inhibiting interneurons that normally inhibit it by binding to their opioid receptors. Nicotine and alcohol are similar, binding to AChR’s and GABA receptors in the same area.

Question 32

Why are heroin, nicotine, and alcohol less addictive than cocaine?

Answer 32

They indirectly modulate the pleasure pathway rather than directly stimulating it.

Question 33

What are treatment strategies for drugs that indirectly modulate the VTA neurons?

Answer 33

Using drugs that are a substitute for the effect, but with less side effects.

Question 34

Describe methadone.

Answer 34

Prevents heroin or morphine from interacting with opioid receptors for instead of natural endorphin painkillers, thus blocking their addictive effect.
It causes mild euphoria and drowsiness, and lasts longer than the heroin (1-2 days) without creating possibly fatal respiratory depression. While weaning off of methadone does cause withdrawal, it is less severe than with heroin.

Question 35

Describe nicotine treatment.

Answer 35

Patches of nicotine are given that produce low levels of nicotine in the blood, rather than the bogus associated with smoking. Patch concentration is reduced over time without producing craving.

Question 36

Describe Antabuse.

Answer 36

For alcohol treatment. It blocks the normal alcohol to acetaldehyde, and acetaldehyde to acetic acid breakdown in the liver at the acetaldehyde dehydrogenase stage. Thus acetaldehyde buildup is so severe that immediate and severe hangover symptoms occur, thus blocking pleasurable response from alcohol consumption.