Cocaine

Question 1

Overall symptoms of taking psychostimulant drugs?

Answer 1

• increase alertness, heighten arousal and behavioral excitement.

Question 2

How can Cocaine HCl be transformed into cocaine freebase?[2]?

Answer 2

• Dissolve cocaine with baking soda, heat and dry.
  
  • “crack” or “rock”
• Dissolve in water, add alkaline(ammonia), extract cocaine base with ether.

Question 3

State the difference in rapid absorption of cocaine with different methods of intake?

Answer 3

• Fastest:
  
  • IV injection and Smoking.
• Slowest:
  
  • Snorting and oral use.

Question 4

Characteristics of cocaine?

• Soluble?
  
  • to BBB?
• half-life?
• breakdown products?
• mixture with alcohol?

Answer 4

• Fat soluble:
  
  • rapidly pass through BBB.
• Half-life:
  
  • 0.5-1.5 hrs.
• Breakdown product:
  
  • Benzoylecgonine: persists in urine for several days.
• Mixture with alcohol:
  
  • Cocaethylene:
    
    • longer half life.

Question 5

Mechanism of Cocaine:

• which transmitters?
• Mechanism of function?
  *

Answer 5

• DA, NE, and 5-HT.
  
  • Highest———–> lowest affinity.

Mechanism:

• block membrane transporters that take up these neurotransmitters:
  
  • therefore:
    
    • allows the presence of these neurotransmitters to increase within the synaptic cleft.

Question 6

State the additional mechanism of action of cocaine at higher concentrations?

Answer 6

• Inhibit voltage-gated Na+ channels in axons , blocking nerve conduction.
  
  • Acting as a local anesthetic.
• Examples:
  
  • Procaine(Novocain) and Lidocaine( Xylocaine).

Question 7

Low dosage in animal models?

• effects when dosage increase?

Answer 7

• increased locomotion, rearing and mild sniffing behaviour.
• Focused stereotypies:
  • when dosage increases, repetitive, seemingly aimless manner
    *

Question 8

Describe Cocaine as a sympathomimetic?

• Difference from a low dose to a high dose?

Answer 8

Produces symptoms of sympathetic nervous system activation:

• ++HR, vasoconstriction, hypertension and hyperthermia.

High doses:

• Seizures, heart failure, stroke ,and intracranial hemorrhage.
  
  • as a result of severe vasoconstriction.

Question 9

What pathway is associated with amphetamines and cocaine?

Answer 9

• Nigrostriatial:
  
  • Substantia nigra—–> striatum.
• Mesolimbic:
  
  • VTA——> NAcc.

Question 10

Significance of the Nucleus Accumbens in cocaine?

Answer 10

• Area associated with Drug-seeking behaviour;
  
  • evidence in microinjection of DA agonists in Nacc.

Question 11

State the effects of D1-D3 genetic knockout on self-administration of cocaine.

• D1?
• D2?
• D3?

Answer 11

D1:

• Knockout: do not self-administer cocaine, suggesting a critical reinforcement.

D2:

• knockout mice do self-administered.

D3:

• KO or antagonist, blocks the reward the effects of cocaine.
  
  • Antagonist: SB-277011.

Question 12

PET scans of Cocaine dependent individuals?

• Labelling of striatal receptors?

Answer 12

• Reduced activity in the striatum in response to drug challenge.
  
  • Striatal DA receptors labelled with raclopride.
• Reduction in D2 receptor binding,
  
  • less responsive to DA reuptake as this contributes to behavioural tolerance.