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Neurobiology of Disease > Drugs of abuse (Nbio) > Flashcards

Drugs of abuse (Nbio) Flashcards

1
Q

What pathways are involved?

A
  • Dopamine and serotonin
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2
Q

What are the functions of the dopamine pathways?

A
  • Reward
  • Pleasure, Euphoria
  • Motor function
  • Compulsion
  • Perserveration
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3
Q

What are the functions of the Serotonin pathways?

A
  • Mood
  • Memory processing
  • Sleep
  • Cognition
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4
Q

What is the mesolimbic dopamine pathways?

A
  • Midbrain ventral tegmental area (VTA) dopamine neurons innervate the nucleus accumbens, part of the limbic system controlling emotion, pleasure, reward and goal-directed behaviour.
  • Overactivity in this pathway contributes to psychosis, delusions and hallucinations: The positve symptoms of schizophrenia.
  • Involved in producing reward and pleasure to encourage to do - Dopamine pathwyas are responsible
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5
Q

What are the brain reward pathways?

A
  1. Common feature many drugs of abuse increase dopamine release in Nuc Acc:
    * Opiates, opiods, Nicotine, Amphetamine, Cocaine etc etc
  2. Others drugs enhance 5-HT function (innervate nuc.ACC)
    * LSD
    * Ecstacy

3.Others block N-methyl-D-Aspartate receptors
* NMDA antagonists (Ket)

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6
Q

Explain a reward experiment with rats

A
  • Activity in VTA dopamine neuronal pathways is associated with reward
  • Rats will self admin rewarding drugs and using microelectrodes
  • Activity can be recorded from dopamine neurons in VTA
  • (rats press a lever that delivers intavenous cocaine)
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7
Q

How does a difference in reward vs expected reward change things?

A
  • A reward that is better than predicted elicits stronger neuronal activation
  • VTA DA neurons respond to unpredicted reward by a phasic short lasting burst of activity which results in DA release from nerve terminals in Nuc.Acc and frontal cortex
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8
Q

What is Microdialysis?

A
  • A technique that allows NT release into the extracellular fluid to be measured in conscious animal brain
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9
Q

What effects do Amphetamines, cocaine, Nicotine and Ethanol on dopamine?

A
  • All drugs enhance DA in the VTA dopaminergic
  • Leading to reward
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10
Q

How do drugs of abuse enhance release of dopamine?

A
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11
Q

What is the common key feature of drug of abuse?

A

The faster, higher and more reliable the elevation in brain dopamine levels, the greater the reward (euphoria) and more likely addiction will occur

  • Formulation is a factor affecting absorption rate - Kinetics
  • Intravenous heroin ‘more addictive’ than methadone by mouth
  • Inhaling cocaine greater reward than chewing coca leaves
  • Smoking cigs greater reward than chewing tobacco
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12
Q

Describe some drugs and their dependance reliability.

A
  1. Narcotic analgesics: Morphine + Heroin
    * Both v.strong degree of dependace liability
  2. General CNS depressants: Ethanol, Barbiturates, Cannabis
    * First 2 strong, cannabis weak
  3. Anxiolytic: Benzodiazepines
    * Strong

4.Psychostimulants: Amph, Cocaine, caffeine, Nicotine, Ecstacy
* Strong,V.S, Weak, V.S, Absent?

5.Psychedelic: LSD
* Weak/absent

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13
Q

What are opiods?

A
  • Morphine/Heroin
  • All agonists at G-protein-coupled opiod receptors
  • Red NT release
  • Cause: Analgesia, euphoria, pve reinf, Respiratory depression

Acute effects
* Euphoria, tranq, miosis

Chronic Effects
* Constipation, depression, insomnia, dependence
* Anhedonia and tolerance

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14
Q

What are withdrawal signs of Opioids?

A
  • Craving, restlessness, insomnia, dependence
  • Cold flashes with goose bumps
  • Major symp 48-72 hours after last dose
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15
Q

What is cocaine?

A
  • Alkaloid
  • Inc catecholamine (DA) NT function by prev DA re-uptake
  • Overactivity of symp system at higher doses: Hypertension, tachycardia, dilated pupil, palpitations
  • Crack-smoked = V.rapid dependence
  • Little tolerance
  • Little physical dependence
  • Strong psychological dependence
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16
Q

What is cannabis?

A
  • Active agent is THC, mimics effects of endogenous endocannabinoids
  • Inhibits wide range of NT release in brain and periphery via specific Gi protein-coupled cannabinoids CB1, CB2
  • Mild euphoric effect in mod doses, Dysphoric in high doses particularly naive uses
  • Very low acute toxicity but concerns about dev of psychosis in chronic heavy users
  • Stim appetite through actions on feeding centres in hypo and possibly gut
    (analgesic activity)
17
Q

What are amphetamines?

A
  • Produce increased wakefulness and conc with decd fatigue and appetite
  • Performance enhancing, some tolerance
  • Release monoamines (DA) from neuronal storage vesicles and block DAT, NET and SERT re-uptake transporters, INC synaptic DA, NA and 5-HT
  • Gives feelings of Euphoria, energy, self-esteem, aggro, obsession and paranoia
  • High/chronic doses can cause psychosis
  • Inc CV tone

Neurobiology of Disease (22 decks)

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