EB - Psychoactive Drugs II

Question 1

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

Answer 1

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• Withdrawn from clinical use in 1965 due to ‘emergence phenomenon)

Question 2

What are the psychological effects of PCP? (7)

Answer 2

• 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

Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

What are the features of drug addiction? (3)

Answer 5

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

Question 6

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

Answer 6

• 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

Question 7

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

Answer 7

• Rats with stimulating electrodes would self-administer electrical stimulation.
• Rats repeatedly stimulated brain regions that gave a pleasurable response (reinforcement behavior).
• The medial forebrain bundle was a key area in the brain for this reward.

Question 8

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

Answer 8

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

Question 9

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

Answer 9

• 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.

Question 10

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

Answer 10

• 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.

Question 11

How does cocaine act as a stimulant and anaesthetic? (5)

Answer 11

• Cocaine acts as a local anesthetic by blocking voltage-gated sodium channels.
• Causes euphoria
• Acts as an appetite suppressant
• Can lead to tremors, convulsions and CNS depression
• Psychosis in susceptible individuals.

LSD has negligible toxicity but cocaine is very toxic

Question 12

How does cocaine affect catecholamine neurotransmission? (2)

Answer 12

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

Question 13

How does cocaine affect dopamine and reinforcement?

Answer 13

• 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.

Question 14

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

Answer 14

• 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.

Question 15

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

Answer 15

• 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

Question 16

Where are D2 receptors mostly located?

Answer 16

Basal ganglia