EB - Psychoactive Drugs II Flashcards

1
Q

What class of drug is Phencyclidine (PCP) and what are its main effects? (3)

A
  • A dissociative anaesthetic (same as ketamine)
  • Causes a catatonic-like state without muscle relaxation
  • Withdrawn from clinical use in 1965 due to ‘emergence phenomenon)
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2
Q

What are the psychological effects of PCP? (7)

A
  • Altered body image
  • Feeling of isolation
  • Cognitive disorganisation
  • Drowsiness and apathy
  • Negativism and/or hostility
  • Euphoria and inebriation
  • Hypnagogic (dreamlike) states

Intoxication associated with drug-induced hallucinations

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3
Q

How does PCP alter perception on a biochemical level? (2)

A
  • PCP interacts with the Sigma-1 receptor, modulating noradrenaline release
    (Didn’t seem to be linked to the hallucination properties)
  • Acts as a non-competitive antagonist at NDMA glutamate receptors
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4
Q

How are psychedelics like LSD and PCP used in disease signalling?

A

Both are used in animal studies to model drug-induced schizophrenia

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5
Q

What are the features of drug addiction? (3)

A
  • Compulsion to take drug
  • Tolerance (decreased response to repeated administration)
  • Withdrawal syndrome (symptoms opposite to drug effects)
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6
Q

how does addiction affect the brain’s limbic system? (3)

A
  • Psychoactive drugs affect areas like the amygdala, ventral tegmental area, and nucleus accumbens
  • These areas are involved in reward and punishment systems, cruicial for motivation and avoidance
  • Innapropriate activation leads to addictive behaviour
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7
Q

What experiment did James Olds and Peter Milner (1954) conduct regarding reward centres in the brain? (3)

A
  • Rats with stimulating electrodes would self-administer electrical stimulation.
  • Rats repeatedly stimulated brain regions, showing reinforcement behavior.
  • The medial forebrain bundle was a key area in the brain for this reward.
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8
Q

What neurotransmitter pathways are involved in the medial forebrain bundle’s reinforcement system? (3)

A
  • Dopaminergic axons from the ventral tegmental area
  • Serotonergic axons from raphe neurons
  • Noradrenergic axons from locus coeruleus neurons
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9
Q

What evidence shows that dopamine is important in reinforcement behaviour? (2)

A
  • Reinforcement was blocked by spiroperidol (a dopamine antagonist that blocks D2 receptors).
  • 6-OH-DA lesions also blocked reinforcement.

This suggests that dopamine is critical in reinforcement behavior.

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10
Q

How are optogenetic techniques used to study reinforcement behaviour? (3)

A
  • Optogenetic techniques offer temporally precise, noninvasive control of activity in specific neural populations using microbial opsins.
  • Optogenetic stimulation of dopamine neurons drives intracranial self-stimulation (ICSS), where animals engage in self-stimulation behavior.
  • This suggests that the reinforcing system involves dopamine axons in the medial forebrain bundle projecting to the nucleus accumbens.
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11
Q

How does cocaine act as a stimulant and anaesthetic? (4)

A
  • Cocaine acts as a local anesthetic by blocking voltage-gated sodium channels.
  • Causes euphoria
  • Acts as an appetite suppressant
  • Can lead to tremors or psychosis in susceptible individuals.

LSD has negligible toxicity but cocaine is very toxic

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12
Q

How does cocaine affect catecholamine neurotransmission? (2)

A
  • Cocaine blocks high-affinity transporters on presynaptic terminals.
  • This prevents recycling of catecholamines, leading to increased levels in the synaptic space.
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13
Q

How does cocaine affect dopamine and reinforcement?

A
  • Cocaine binds with high affinity to dopamine transporters, preventing dopamine reuptake.
  • Experiment 1: Mice with DA transporter knockouts do not show additional elevated dopamine levels but still self-administer cocaine.
  • Experiment 2 (more refined): Mice with cocaine-insensitive DAT knock-in (F105 mutation) did not show elevated dopamine or reinforcement (no CPP), indicating that dopamine elevation is necessary for cocaine’s reinforcing effects.
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14
Q

How is PET imaging used to study cocaine’s effects on dopamine in humans? (2)

A
  • PET imaging with 11C-raclopride is used to label D2 receptors in the brain.
  • This technique helps study how cocaine affects dopamine signaling and receptor availability in humans.
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15
Q

What happens to D2 receptors in cocaine abusers? (2)

A
  • Cocaine abusers show downregulation of D2 receptors.
  • This alteration in the reward system remains even after detoxification

All humans have a D2 receptor decrease as we get older but a lot of variability

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16
Q

Where are D2 receptors mostly located?

A

Basal ganglia