Cocaine

Cocaine Def

Natural insecticide found in certain leaves (which contain approx .75% cocaine)

3 Forms

3 Forms of Cocaine

1. Coca Paste

2. Cocaine Hydrochloride

3. Cocaine Base

Coca Paste

Extract from the leaves

40-85% cocaine

Cocaine Hydrogenase

Powdered form of coca paste; Hydrochloric salt makes it hydrophilic

Cocaine Base

Crystallized form of powdered cocaine

Can be heated up, unlike powder

Routes of Absorption for Coca Leaf

TM or O through chewing

Routes of Absorption for Cocaine Hydrochloride

TM through snorting + IV

Routes of Absorption for Coca Paste + Coca Base

IH through smoking

Cocaine + TM Absorption

Cocaine constricts blood vessels, which limits TM

Which route of absorption has the shortest effect for cocaine?

Smoking (inhaling/tm)

Is cocaine hydrophilic or lipophilic?

Lipophilic

Easily crosses BBB

What happens to the hydrochloride salt on powdered cocaine?

Dissociates in the blood

How much higher is concentration in the brain than blood for cocaine?

7 times

What is cocaine’s half-life?

Short

Approx 50 mins

Where is cocaine broken up?

1. Blood

2. Liver

Broken down by the enzyme butrylcholinesterase into benzolyecgonine

Butrylcholinesterase

The enzyme that actually breaks cocaine down

Benzolyecgonine

What cocaine is broken down into

Can be very toxic

Cocaethylene

What is produced if cocaine is combined with alcohol after metabolism; Acts on same targets + stays in body 3x longer

Lasts longer in the brain bc it has a higher concentration

Higher half-life; 150 ish mins

Excretion + Cocaine

Detected in sweat weeks after use

Detected in urine + blood for 12 hours

Metabolite can be detected for 48 hours

In hair for months

What does cocaine act as?

Reuptake Inhibitor (blocks transport back into presynaptic neuron)

Neurotransmitters Cocaine acts on

• Epinephrine

• Norepinephrine

• Serotonin

• Dopamine (MOSTLY THIS)

Cells cant pick these up again

Nucleus Accumbens

Associated with drugs of abuse; What cocaine acts through

Evidence for Dopamine + Nucleus Accumbus for Cocaine

1. Dopamine Antagonists

2. Immunoflourence

3. Lesions to Nucleus Accumpus (more dopamine = more cocaine seeking)

4. Optogenetic Inhibition of Nucleus Accumbus

Dopamine Antagonists (Cocaine)

Block cocaine seeking behavior

Evidence for Dopamine + Nucleus Accumbus

Immunofluorescence (Cocaine)

Identifies dopamine receptors in nucleus accumbus in rats

Evidence for Dopamine + Nucleus Accumbus

Lesions to Nucleus Accumbus (Cocaine)

Influence cocaine taking behav depending on remaining dopamine levels

More dopamine = more cocaine seeking

Evidence for Dopamine + Nucleus Accumbus

Optogenetic Inhibition of Nucleus Accumbus (Cocaine)

Reduces cocaine seeking behav

Evidence for Dopamine + Nucleus Accumbus

Cocaine + Serotonin in Living

More cocaine = Less serotonin

Cocaine + Serotonin in Dead

No effect on serotonin

Do ions cross BBB easily?

No

How does higher cocaine dose impact permeability + BBB?

Increases permeability + more ions enter BBB over time

Effects of Cocaine on Rest of Body

• Total Analgesic (reduces pain)

• Norepinephrine stimulates fight/flight

• Feelings of euphoria

• Aggression

• Paranoia

• Increased sexual libido

• Increased alertness

• Lower appetite

• Increased locomotion (including more speech)

What can chronic cocaine use do to reward circuits?

Alters them so it makes cocaine more appealing/addictive after a few uses

Chronic Cocaine Use Symptoms

• Aud + tactile hallucinations (formication)

• Anhedonia + irritability when not using

• Risk of cardio disease

• Reduction in gray matter + associated with drop in cog function (can be reversed after stopping)

• Changes in dopamine signaling

Formication

Feeling of ants crawling all over you

Chronic cocaine use

Anhedonia

Lack of pleasure

Chronic cocaine use

Gray Matter

Regions with cell bodies

Reduces with chronic cocaine use

Changes in Dopamine Signaling with Chronic Cocaine Use

Increased sensitivity of D1 receptors

Decreased sensitivity of D2 receptors

D1 Receptors

Excite dopamine

D2 Receptors

Inhibit dopamine

2 Drugs that can disrupt the BBB

1. Cocaine

2. Amphetamines

Makes it more permeable so more ions can get in

Can stopping cocaine reverse effects?

Yes