Week 8 CNS stimulants and drugs of abuse

Question 1

What drugs are under the category of methylxanthines?

Answer 1

• theophylline in tea
• theobromine in chocolate
• caffeine

Question 2

How does caffeine act on the brain?

Answer 2

• adenosine is a neuromodulator that accumulates during fatigue, it binds to receptors in the brain to inhibit the release of NTs to prepare it for rest
• caffeine blocks all types of adenosine receptors which leads to increase firing of neurons and brain activity
• cause the pituitary gland to release hormones like ACTH which prompt adrenal glands to release adrenaline

Question 3

What is the mechanism of LSD (lysergic acid diethyl amide)?

Answer 3

• serotonin agonist at presynaptic receptors in midbrain
• activates sympathetic nervous system
• cause hallucinations and mood alterations
• hallucinations may be rapidly aborted by haldoperidol-antipsychotic agent

Question 4

What is the mechanism of THC?

Answer 4

-binds to cannabinoid receptors (presynaptic CB1) and inhibit release of NT such as glutamate, DA, GABA

Question 5

Classify addictive drugs based on their molecular argot and underlying mechanism of action.

Answer 5

1. Drugs that act via G coupled protein receptors: Opioids, cannabinoids, GHB, hallucinogens
2. Drugs that act via ion channels: nicotine, benzodiazepines, alcohol
3. Drugs that alter MAO neurotransmission: cocaine, amphetamines, ecstasy, bath salts

Question 6

How do addictive drugs alter the mesolimbic dopamine system?

Answer 6

-nicotine: depolarizes DA neurons increasing DA release
-Opioids, GHB: block inhibition of local GABA neurons, increasing DA release
-cocaine, amphetamines: block DAT increasing DA concentration in the synapse
Summary: increase DA concentrations in the target structures of the ventral segmental area (VTA) in the midbrain
-targets of VTA include: nucleus accumbens, prefrontal cortex, amygdala, and lateral hypothalamus
-prolonged stimulation of positive prediction error

Question 7

What are the effects of drug abuse on down stream signaling pathways?

Answer 7

• stimulates deltaFosB, which leads to stable long term changes in neurons by promoting expression of Cdk5 in stratal neurons to promote axon growth and new spine formation
• Cdk5 linked to increase in spine density on target neurons of nuc. accumbens, and prefrontal cortex following chronic cocaine use

Question 8

How is drug induced aberrant neuroplasticity changed by drug withdrawal?

Answer 8

• LTP at VTA dopaminergic neurons remains potentiated even after drug seeking behaviors are extinguished
• over time, depression in synaptic transmission reverses into synaptic potentiation so that behavioral cues previously associated with availability of drug leads to increased efforts to obtain drug
• susceptibility and sensitivity to drug associated sensory cues that lead to intensified drug craving for weeks to months after drug withdrawal