Reward and drugs of abuse

Question 1

Define reinforcing

Answer 1

1. REINFORCING: something is reinforcing when an animal will perform a behaviour in order to obtain that stimulus. ie. It is rewarding.

Question 2

What is euphoria

Answer 2

1. A feeling of great happiness or well-being

Question 3

What is psychological dependence

Answer 3

1. Psychological dependence: Craving, compulsive drug use, loss of control, ‘addiction’

Question 4

What is physical dependence

Answer 4

1. Physical dependence: When stopping a drug causes a withdrawal syndrome

Question 5

What is tolerance

Answer 5

1. Tolerance: When continued use of a drug results in the need for increasing doses for equivalent effect

Question 6

What is the biological basis for reward

Answer 6

1. Olds & Milner (1954) first identified brain sites where direct electrical stimulation is reinforcing
2. What they did - intra-cranial self-stimulation (ICSS):
3. Implanted electrodes into different parts of rat brains.
4. When the rat pressed a lever, received electrical stimuli directly into that brain region.
5. mesolimbic pathway- projects to ventral striatum
6. If electrode activated induced action potential in this collection of neurons the rats would press the lever

Question 7

Describe results of experiments with mesolimbic pathway

Answer 7

1. Rats will CONTINUALLY self-stimulate to activate the mesolimbic pathway
2. When given the choice between obtaining food and water or electrical brain stimulation of mesolimbic pathway. Rats choose stimulation even until death.
3. Limited studies in humans. But some:
   - Injected electrodes into them asked someone to stimulate- continually asked
   - Felt in love with person

Question 8

How can you find what neurotransmitters are present in the mesolimbic pathway

Answer 8

1. Intercranial self stimulation using microdialysis
2. Used to sample neurotransmitters that have been released from nerve terminals
3. Implant micro dialysis probe in the nucleus accumbens
4. Has semi permeable membrane
5. If nerve terminals stimulated neurotransmitter passes into dialysis and is pumped up
   e)

Question 9

What is the neurotransmitter present in nucleus accumbens

Answer 9

1. Dopamine is neurotransmitter
2. Dopamine is released by ICSS (intracranial self stimulation)
3. Dopamine D1 OR D2 antagonists administered directly into nucleus accumbens reduce ICSS

Question 10

Can animals self-administer drugs of abuse

Answer 10

1. Animals will self-administer drugs of abuse- icv (intracerebroventricular injections)
2. Linked to pump
3. If animal presses lever they get drug
4. If reinforcing they will continue to push lever

Question 11

Is the mesolimbic pathway involved with drugs of abuse?

Answer 11

1. 6-OHDA (Chemical lesion of mesolimbic pathway)- selectively kills dopamine neurons
2. Animals won’t self-administer if 6-OHDA has destroyed neurons
3. D1 and D2 antagonists inhibit drug self-administration

Question 12

What do drugs of abuse cause the increase of

Answer 12

1. Probe inserted into rat nucleus accumbens
2. Injected with different drugs
3. Huge increase in dopamine with each drug
4. Disphoric drug- kappa receptor agonists- causes decrease of dopamine in nucleus accumbens

Question 13

How does dopamine and amphetamine increase DA levels in NAcc

Answer 13

1. Increase DA release or inhibit re-uptake
2. Dopamine is terminated by uptake importers
3. They inhibit the transporter
4. Dopamine hangs around in synaptic cleft for longer
5. Amphetamine also is thought to cause reverse transport
   - Allows dopamine inside the cell to leak out into synaptic cleft

Question 14

How do opioids increase DA levels in NAcc

Answer 14

1. act on mu-opioid receptors on GABAergic neurones.
2. Cause disinhibition (release of an inhibitory constraint that effectively results in an increased activity in the target neurons) of DA neurones in VTA- ventral tegmental area
3. Inhibitory gabaergic interneuron
4. Mu opioid receptors- gi/o coupled- inhibitory
5. Disinhibition - Inhibiting a neuron which normally inhibits
6. morphine, heroin, methadone, oxycodone

Question 15

How does ethanol increase DA levels in NAcc

Answer 15

1. acts directly on DA neurones in VTA.
2. Decreases AHP- afterhyperpolarisation, increases firing rate
3. Acts as potassium channel blocker so increases firing rate
4. After hyperpolarisation is shorter and smaller
5. unpotent

Question 16

How does nicotine increase DA levels in NAcc

Answer 16

1. acts on nicotinic acetylcholine receptors on DA neurones in VTA.
2. Increases firing rate

Question 17

How does cannabis increase DA levels in NAcc

Answer 17

1. THC: acts on cannabinoid receptors on GABAergic neurones.

2. Similar to Opioid receptors- Gi/o coupled etc

Question 18

What is the VTA

Answer 18

1. The ventral tegmental area (VTA) is a structure in the midbrain which sends dopaminergic neural projections to both the limbic and cortical areas

Question 19

What else does ethanol do

Answer 19

1. Does lots of things: of different importances in different parts of the brain at different doses
2. Decreases After-Hyperpolarization (AHP)
3. GABAA allosteric modulator
4. NMDA receptor antagonist
5. Calcium channel antagonist