PSYCHOMOTOR STIMULANTS CHAP 12

Question 1

List 7 background information on cocaine.

Answer 1

1. Cocaine: alkaloid in leaves of the shrub Erythroxylon coca native to South America
2. The practice of chewing coca leaves began 5000 years ago.

3.Pure cocaine isolated in 1850s; there were many famous users, including Freud

4.Cocaine was used in many medications— tooth drops to infant

5.Coca Cola was introduced in 1886 (cocaine + caffeine)

6.Cocaine abuse became widespread; prohibited cocaine in OTC medicines

7.Cocaine use by snorting or IV injection increased in the 1970s; more recently, “crack” cocaine became popular

Question 2

How is cocaine produced?

Answer 2

Cocaine is extracted from coca leaves, converted to a
hydrochloride (HCl) salt and crystallized

Question 3

describe the administration of cocaine.

Answer 3

Cocaine HCl is water-soluble and thus can be taken orally, intranasally (snorting), or by IV injection; can not be smoked

Question 4

How can cocaine HCl be smoked?

Answer 4

when transformed back into cocaine that can be
smoked by two methods:
– Freebasing
– Crack

Question 5

explain the absorption of cocaine with respect to administration.

Answer 5

Extremely rapid absorption occurs with IV injection and smoking; slower with snorting and oral use

Question 6

what happen when cocaine is absorbed? What is seen after?

Answer 6

1. Once absorbed, cocaine is rapidly broken down and excreted; the subjective high lasts about 30 minutes
2. Metabolites such as benzoylecgonine can be detected in the urine for several days

Question 7

what is seen when alcohol and cocaine are used at the same time?

Answer 7

Cocaine plus alcohol produce a unique metabolite called cocaethylene – has activity similar to cocaine and longer half life

Question 8

What is most of cocaine actions due to? and what does the cause?

Answer 8

due to its ability to block reuptake of DA, NE, and 5-HT by inhibiting their membrane transporters; increased synaptic concentrations of transmitters

Question 9

describe cocaine’s affinity to certain transporter.

Answer 9

Has higher affinity for the 5-HT and NE transporters than for the DA transporter

Question 10

what effect does DA have on cocaine properties?

Answer 10

Blockade of DA reuptake is most important for cocaine’s stimulating, reinforcing, and addictive properties

Question 11

what similar process happen at serotonergic and noradrenergic synapses because of cocaine?

Answer 11

A similar process to the blockade of DA transporters occurs at serotonergic and noradrenergic synapses because of cocaine’s inhibition of 5-HT and NE reuptake.

Question 12

what are the negative findings about glutamate?

Answer 12

High levels of glutamate can be toxic to nerve cells

Question 13

what is excitotoxicity hypothesis?

Answer 13

excessive exposure to glutamate causes prolonged depolarization of receptive neurons that leads to their damage or death.

Question 14

what is excitotoxic lesions?

Answer 14

are selective: kills nerve cells but spares fibers of
passage

Question 15

what are three main causes of cell death?

Answer 15

Cell death can occur by necrosis, characterized by lysis, or by programmed cell death (apoptosis – disruption of the nucleus and DNA breakdown; programmed necrosis/necroptosis)

Question 16

Explain cell death by necrosis in three steps.

Answer 16

1.During the initial stages of necrosis, the cell
swells and the membrane forms protrusions
called blebs.

2. In the next stage (B), the
   membrane begins to break up and release the
   contents of the cell cytoplasm.

3.Finally, the cell disintegrates completely (C).

Question 17

Explain cell death by necrosis in three steps.

Answer 17

1. In apoptotic cell death, the cell also blebs
   but instead of swelling, it shrinks.

2.At the same time, the chromatin (genetic material)
condenses within the cell nucleus. The cell then
breaks up into smaller pieces

3.they are then subsequently engulfed and digested by
phagocytes (F)

Question 18

how is GABA synthesized? from what amino acid is it synthesized?

Answer 18

GABA is synthesized by the enzyme glutamic acid decarboxylase

Synthesized from glutamate in one step by glutamic acid decarboxylase (GAD)

Question 19

what is GABA?

Answer 19

GABA (γ-aminobutyric acid) major inhibitory amino acid
transmitter; manufactured only by GABAergic neurons; has a critical role in regulating brain excitability.

Question 20

what can block GABA synthesis. give three examples.

Answer 20

1.Allylglycine
2.thiosemicarbazide
3. 3-mercaptopropionic acid can block GABA synthesis

Question 21

what studies can only use GABA blocker?

Answer 21

can only be used for in vitro studies

Question 22

What transporter proteins pack GABA into vesicles and uptake after release?

Answer 22

Vesicular GABA transporters (VGAT) move GABA (and glycine) into vesicles

Question 23

give three examples of what transporter remove GABA from the synaptic cleft? where are these transporter located?

Answer 23

GABA is removed from the synaptic cleft by transporters GAT-1 and GAT-2 (in neurons and astrocytes) and GAT-3 (only in astrocytes)

Question 24

what is the purpose of Tiagabine?

Answer 24

selective inhibitor of GAT-1; elevates extracellular GABA levels and enhances GABAergic transmission in several brain areas

Question 25

what is tiagabine good for treating?

Answer 25

marketed as Gabitril for treating epilepsy

Question 26

with what enzyme does GABA metabolize and what does it metabolize into?

Answer 26

GABA is metabolized by GABA aminotransferase (GABA-T), in neurons and astrocytes to form glutamate and succinate

Question 27

what is the process of making GABA? Explain in two steps.

Answer 27

1. In astrocytes, the glutamate is converted to glutamine by glutamine synthetase
2. Glutamine can be released by astrocytes, taken up by neurons, converted back to glutamate, and used to remake GABA

Question 28

What is GABA co-released with?

Answer 28

Co-release of GABA has been demonstrated for neurons that also use glycine, ACh, DA, or glutamate

Question 29

what can you say about co-expression with respect to GABA?

Answer 29

Some neurons co-release GABA (inhibitory) and glutamate (excitatory) at the same time; allows for fine-tuning of the postsynaptic response.

Question 30

Give three examples of co-transmission of GABA with other neurotransmitter. Also, list the vesicular transporter associated with the neurotransmitters. Give three examples?

Answer 30

1. ACh(VAChT) and GABA(VGAT)
2. DA/GABA(VMAT2)
   3.Glu/GABA(VGLUT2/VGAT)

Question 31

what kind of neurons are GABAergic?

Answer 31

Some GABAergic neurons are interneurons, while others are projection neurons

Question 32

What brain areas are rich with GABA. Give 4 locations and their respective neurons associated with them.

Answer 32

1.Cortex and hippocampus: GABAergic neurons are interneurons

2. Striatum and cerebellar Purkinje cells: projection neurons

Question 33

how are the actions mediated by for GABA?

Answer 33

The actions of GABA are primarily mediated by ionotropic GABAA receptors

Question 34

What is the ionotropic receptor called for GABA?

Answer 34

GABAA receptor—ionotropic

Question 35

how many subunits is GABAA receptor composed of? what are they?

Answer 35

Each receptor is composed of five subunits, usually two α subunits, two βs, and one γ

Question 36

what does GABAA receptor do?

Answer 36

GABAA channel allows Cl–to move in, causing hyperpolarization and inhibition of the postsynaptic cell

Question 37

what is Muscimol?

Answer 37

GABAA agonist from the mushroom Amanita muscaria

Question 38

what is Bicuculline?

Answer 38

competitive antagonist for GABAA receptors; blocks binding of GABA; if taken systemically, causes convulsions.

Question 39

what does Pentylenetetrazol (Metrazol) and picrotoxin do?

Answer 39

convulsant drugs that inhibit GABAA receptor function; act at sites distinct from the GABA binding site (noncompetitive antagonists)